Cancer Letters 361 (2015) 8–12

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Cancer Letters j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / c a n l e t

Mini-review

MicroRNAs-mediated cell fate in triple negative breast cancers Xinbing Sui a,b, Xian Wang a,b, Weidong Han a,b, Da Li a,b, Yinghua Xu a, Fang Lou a, Jichun Zhou c, Xidong Gu d, Jing Zhu e, Cheng Zhang f, Hongming Pan a,b,* a

Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China d Department of Breast Surgery, The First affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China e Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China f Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China b c

A R T I C L E

I N F O

Article history: Received 16 December 2014 Received in revised form 26 February 2015 Accepted 26 February 2015 Keywords: MicroRNA Cell fate Triple negative breast cancer

A B S T R A C T

MicroRNAs (miRNAs) are small non-coding RNAs that function as major modulators of posttranscriptional protein-coding gene expression in diverse biological processes including cell survival, cell cycle arrest, senescence, autophagy, and differentiation. The control of miRNAs plays an important role in cancer initiation and metastasis. Triple negative breast cancer (TNBC) is a distinct breast cancer subtype, which is defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu). Due to its high recurrence rate and poor prognosis, TNBC represents a challenge for breast cancer therapy. In recent years, a large number of microRNAs have been identified to play a crucial role in TNBC and some of them were found to be correlated with worse prognosis of TNBC. Thus, understanding the novel function of miRNAs may allow us to develop promising therapeutic targets for the treatment of TNBC patients. © 2015 Elsevier Ireland Ltd. All rights reserved.

Introduction Breast cancer is the most common malignancy among the women worldwide and usually classified according to the different expression levels of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu) [1–3]. Triple negative breast cancer (TNBC) represents a high invasive clinical subtype of breast cancer, which is characterized by the absence of ER, PR and HER2 [4]. TNBC patients show higher recurrence rate and poorer prognosis compared to other breast cancer subtypes. Due to its gene expression, targeted therapies are not available for TNBC. The only treatment strategy for TNBC is chemotherapy [5]. Moreover, the therapeutic drugs for TNBC are very limited and only a few chemotherapeutic agents (such as anthracyclins, taxanes and platinum agents) are proved to be useful in TNBC, since it is often resistant to conventional and moderate chemotherapy drugs [6]. In addition to chemotherapeutic agents, some other experimental therapeutic approaches are involved in TNBC treatment. Growth hormone–releasing hormone (GHRH) antagonists were proved to reduce tumor growth by tumoral GHRH receptors, therefore, they could facilitate the development of new strategies for the TNBC treatment [7]. XBP1 activation of the unfolded protein (UPR)

* Corresponding author. Tel.: +86 0571 86006926; fax: +86 0571 86006926. E-mail address: [email protected] (H. Pan). http://dx.doi.org/10.1016/j.canlet.2015.02.048 0304-3835/© 2015 Elsevier Ireland Ltd. All rights reserved.

promoted the tumorigenicity and progression of TNBC, implying that UPR inhibitors in combination with standard chemotherapy may improve the effectiveness of anticancer therapies [8]. In the absence of approved targeted agents for the treatment of TNBC, some new targeted agents are going on experimental trials [9]. However, there are no standard treatment guidelines for TNBC up to date. Therefore, new therapeutic targets for TNBC need to be identified. MicroRNAs (miRNAs) are small non-coding RNA molecules of 21–24 nucleotides in length that can regulate the posttranscriptional protein-coding gene expression, and are involved in diverse biological processes including cell survival, cell cycle arrest, senescence, autophagy, differentiation, and metastasis [10,11]. An increasing body of evidence suggests that miRNAs play a double role in the different steps of cancer, behaving both as oncogenes or tumor suppressor genes [12]. The oncosuppressive miRNAs exhibit antitumor effect on cancer cells. In contrast, oncogenic miRNAs (oncomiRs) contribute to the initiation and progression of diverse malignancy types such as breast cancer [13,14]. Currently, there is increasing evidence to suggest that microRNAs may provide correlations with the diagnosis, prognosis and treatment of breast cancer [15,16]. The serum levels of miR-155, miR-19a, miR-181b, miR-24, and miR-484 are significantly more abundant in early-stage breast cancer (EBC) patients compared to controls at the time of diagnosis and testing these oncomiRs may be of significant benefit to the diagnosis and relapse detection of EBC patients [17,18]. miR-124 is demonstrated to inhibit breast cancer cell growth and

X. Sui et al./Cancer Letters 361 (2015) 8–12

migration via the regulation of FLOT1 [19]. miR-149 is also shown to suppress breast cancer cell migration/invasion and metastasis by targeting GIT1 [20]. In addition, epigenetic silencing of miR-375 could cause the upregulation of IGF1R, resulting in the resistance of trastuzumab for treating HER2-positive breast cancers and overexpression of miR-375 restored the sensitivity of these cells to trastuzumab [21]. Overall, these data show that miRNAs can be used as diagnostic, prognostic and predictive biomarkers for breast cancer and exploring miRNA expression profiles are attracting more and more attention. Recently, it has been demonstrated that the there is a significant correlation between the expression of miRNAs and TNBC. A large number of miRNAs have been firmly demonstrated to be involved in the initiation and progression of TNBC [22,23]. Moreover, several recent studies are attempting to differentially evaluate the gene and miRNA profiles to predict response to therapy and discriminate different subgroups of TNBC [24,25]. Many microRNAs have been described with the main biological outputs related to TNBC (Fig. 1). These miRNAs not only contribute to the comprehension and subclassification for TNBC, but, more importantly, they also function as potential biomarkers to predict efficacy of anticancer drugs and cancer prognosis. Thus, exploring miRNA expression profiles and defining their possible roles in different TNBC subtypes may allow us to develop a promising therapeutic strategy to improve clinical outcomes in the treatment of TNBC patients. Oncosuppressive miRNAs and TNBC Some miRNAs have been found to function as tumor suppressors inducing tumor cell apoptosis and differentiation in triple negative breast cancer (Fig. 1). The miR-200 family is a well known positive regulator of well-differentiated epithelial phenotype and their expression levels were found to be obviously lower in TNBC cells

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than other types of breast cancer. miR-200b significantly reduced TNBC cell migration and inhibited tumor metastasis by targeting protein kinase Cα (PKCα) [26,27]. miR-200c was reported to maintain the epithelial phenotype not only by targeting PTEN/Akt signaling but also by actively repressing a program of mesenchymal and neuronal genes involved in cell motility and anoikis resistance [28,29]. MicroRNA-200c was also found to suppress proliferation and promote apoptosis of triple negative breast cancer cells by targeting the expression of X-linked inhibitor of apoptosis (XIAP) [30]. In addition, miR-200c was demonstrated to enhance anoikis sensitivity to TNBC cells by directly targeting NF-κB up-regulated TrkB/NTF3 autocrine signaling and inhibition of NF-κB activity repressed anoikis resistance [31]. Finally, the MiR-200 family is also down-regulated in cancer stem-like cells (CSCs) from triple-negative breast cancer patients and reintroduction of miR-200 in combination with conventional chemotherapy may serve as an effective strategy to treat aggressive TNBC [32]. Therefore, miR-200 family may serve as therapeutic approaches for metastatic TNBC. miR-31 plays a specific anti-metastatic role in breast cancer via coordinate repression of a cohort of metastasis-promoting gene RhoA [33]. Loss of miR-31 expression in TNBC cell lines is attributed to hypermethylation of its promoter associated CpG island, resulting in breast cancer progression [34]. miR-34a, a potent endogenous tumor suppressor, is often down regulated in TNBC cells, resulting in the inhibition of cell growth and migration via p53 transcriptional network and a Notch-1-signaling pathway [35–37]. Interestingly, there is also a conflicting report regarding the potential role of miR-34a. Mackiewicz et al. demonstrated that miR-34a expression did not result in apoptosis and cell cycle arrest in TNBC cell lines, conversely, it had pro-oncogenic properties in TNBC [38]. So the function of miR-34a awaits further experimentation. miR-139-5p was significant enrichment in breast cancer metastasis and overexpression of miR-139-5p inhibited the cell motility

Fig. 1. Schematic depiction of the tumor suppressive and pro-tumorigenic roles of microRNAs in triple negative breast cancer. A. Oncosuppressive miRNAs suppress cell proliferation and invasion and promote apoptosis of triple negative breast cancer cells by targeting the expression of some key proteins. B. Oncogenic miRNAs function to promote cell proliferation, invasion and EMT via special targets, resulting in the relapse and development of TNBC.

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and invasion of TNBC [39]. miR-193b increased metformin-induced apoptosis in TNBC cells [40]. miR-203 could function as a tumor suppressor to suppress cell proliferation and migration by targeting BIRC5 and LASP1 in human triple negative breast cancer cells [41]. miR-205, a novel transcriptional target of p53, is often absent in TNBC compared to a normal-like cell line and re-expression of miR-205 strongly reduced cell proliferation, cell cycle progression and clonogenic potential in vitro, and inhibited tumor growth in vivo, at least partially through targeting of the two newly identified target genes, E2F1 and LAMC1 [42,43]. miR-206 repressed tumor cell migration through direct targeting of the actin-binding protein Coronin 1C (CORO1C) in TNBC [44]. miR-342 expression was shown to be highest in ER and HER2/neu-positive luminal B tumors and lowest in TNBCs, which could present an attractive target for therapeutic intervention [45]. In addition, the let-7 miRNA family is known to act as tumor suppressors in breast cancer and several let-7 miRNAs may induce tamoxifen sensitivity by downregulation of estrogen receptor α signaling in TNBC cell lines [46]. Lin28A and Lin28B were also reported to inhibit let-7 miRNA biogenesis by distinct mechanisms [47]. Recently, a functional variant in a let-7 miRNA complementary site in the 3′-untranslated region of the KRAS oncogene was identified to be associated with development of triple-negative breast cancer in premenopausal women [48]. Taken together, these findings shed light on the possible roles and mechanisms of oncosuppressive miRNAs in TNBC.

Oncogenic miRNAs and TNBC In addition to oncosuppressive roles, miRNAs can also act as oncogenes (Fig. 1). miR-9 was reported to be associated with epithelial–mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotypes and high level of miR-9 expression was found to be an independent prognostic factor for poor disease-free survival of TNBC patients [49]. Hyaluronan–CD44 interaction induced c-Jun signaling and miR-21 expression leading to Bcl-2 expression and chemoresistance in triple negative breast cancer cells [50]. High expression of miR-21 was correlated with a poor prognosis of TNBC and upregulated miR-21 promoted TNBC cell proliferation in vitro [51]. Increased expression of miR-15a, miR-15b, miR-16 and miR128 was involved in Smurf2 downregulation in TNBC cell lines, which have mutations in the retinoblastoma (RB) gene [52]. miR-93 expression level in TNBC tissues was significantly higher than that in non-TNBC tissues and ectopic transfection of miR-93 promoted cell proliferation, invasion, and metastasis [53]. miR-145 regulated cell invasion via targeting ADP-ribosylation factor 6 (Arf6) [54]. miR-146a and miR-146b-5p negatively regulated BRCA1 expression, which was accompanied by an increased proliferation and a reduced homologous recombination rate in TNBC [55]. Upregulation of miRNA-155 promoted tumor angiogenesis through targeting von Hippel–Lindau tumor suppressor (VHL) and was associated with poor prognosis of TNBC [56]. miR-155-mediated loss of CCAATenhancer binding protein beta (C/EBPβ) also promoted TNBC progression by shifting the TGF-β response from growth inhibition to epithelial–mesenchymal transition (EMT), invasion and metastasis [57]. miR-181a/b were overexpressed in more aggressive breast cancers, particularly triple negative breast cancers, and deregulated expression of miR-181a/b determined the sensitivity of TNBC cells to the poly-ADp-ribose-polymerase1 (pARp1) inhibition [58,59]. miR-182 expression was significantly increased in the TNBC tissues and inhibition of miR-182 expression resulted in significantly decreased cell proliferation and increased levels of apoptosis in TNBC cells [60]. Finally, miR-221 was demonstrated to function as an oncogene and be essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo [61]. These studies unravel new targets

and/or molecular pathways which are involved in transcriptional control of oncogenic miRNAs in TNBC. Diagnostic, prognostic or therapeutic potential of miRNAs in TNBC miRNA signatures distinguish TNBC from other breast cancer subtypes It has been identified that miRNA aberrant expression could clearly separate breast cancer specimens versus normal tissues. Signatures of differentially expressed miRNAs reveal significant differences between TNBC and other breast cancer subtypes [62]. Triple negative breast patients are demonstrated to have increasing expression of the mir~17–92 cluster, which is significantly distinct from other tumor subtypes [63]. Savad et al. analyzed the expression of miR-21, miR-205, and miR-342 in 59 patients with breast cancer and found that miR-205 and miR-342 expressions were significantly down regulated in the triple negative group compared to other breast cancer groups, suggesting that miR-205 and miR-342 may be used as potential biomarkers for diagnosis of TNBC [42]. The expression of miR-93 was assessed by in situ hybridization in breast cancer. As a result, the miR-93 expression level in TNBC tissues was significantly higher than that in nontriple-negative breast cancer tissues [53]. Calvano Filho et al. reported that there was enhanced expression of miR-17-5p, miR18a-5p, and miR-20a-5 in TNBC compared with luminal A breast cancer [64]. Recently, 4-miRNA signatures (miR-155, miR-493, miR-30e and miR-27a) were also identified as novel diagnostic biomarkers in TNBC [65]. Taken together, these findings elucidate the role of miRNAs as diagnostic biomarkers in TNBC. miRNAs hold potential as prognostic or therapeutic markers in TNBC Early metastasis is a leading cause of TNBC-associated death and the lack of highly sensitive and specific prognostic markers is a major obstacle for effective therapy against TNBC. Recently, several studies have identified miRNAs as prognostic or therapeutic markers in TNBC. A number of known oncogenic microRNAs have been identified to have prognostic potential for TNBC patients, including miR-27b-3p, miR-21, miR-210. Overexpression of miR-27b-3p was confirmed to be an independent predictor for distant metastasis of TNBC patients [66]. High expression of miR-21 and miR-210 posed a positive correlation with poor prognosis for TNBC patients [51,67]. In contrast, some oncosuppressive miRNAs are negatively correlated with the prognosis of TNBC. Farazi et al. indentified distinct miRNA target regulation between breast cancer molecular subtypes by using AGO2-PAR-CLIP and patient datasets. They showed that high expression of miR-17, miR-19a, miR-25 and miR-200b in TNBC were associated with leukocyte transendothelial migration pathway, revealing potential therapeutic targets and prognostic markers for TNBC patients [68]. miR-34b expression negatively correlated with disease free survival (DFS) and overall survival (OS) in TNBC, thus, miR-34b could present a new promising prognostic biomarker in TNBC patients [69]. Decreased expression of the miR-200 family and the miR-17–92 oncogenic cluster was associated with lymph node metastases in triple negative breast cancer [70]. In summary, these data describe predictive interactions between miRNAs and TNBC. Besides the prognostic miRNAs described earlier, there are also other miRNAs involved in the therapeutic implications of TNBC. The result from Kolacinska et al. indicate that higher miR-200b-3p, miR-190a and lower miR-512-5p expression levels in TNBC patients may be associated with better pathologic response to preoperative chemotherapy [71]. Decreased miR-206 expression led to fewer apoptotic BRCA1 wild-type TNBC cells than BRCA1-mutated cells

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when these cells were treated with gemcitabine in combination with the PARP1 inhibitor [72]. miR-31 sensitized TNBC cell MDA-MB-231 to anti-cancer treatments by direct targeting of protein kinase C epsilon (PKC epsilon) [73]. miR-34a can regulate therapy resistance by targeting HDAC1/HDAC7-HSP70 K246 axis, which identifies a viable target for potential new anti-cancer therapies to reduce such resistance in breast cancer [74]. Overexpression of miR-130a-3p or miR-451a in MDA-MB-231 cells significantly enhanced the cells sensitivity to doxorubicin [75]. In addition, miR-200c targets a NF-κB up-regulated TrkB/NTF3 autocrine signaling loop to enhance anoikis sensitivity in TNBC cells [31]. miR-638 overexpression increased sensitivity to DNA-damaging agents ultraviolet (UV) and cisplatin in triple negative breast cancer [76]. Taken together, miRNAs may serve as a potential therapeutic target for TNBC patients. Conclusions Triple negative breast cancer is a heterogeneous subtype of breast cancer and often lacks an effective targeted therapy. It has been suggested that miRNAs may function as therapeutic targets for TNBC. Moreover, a growing body of evidence has demonstrated that miRNAs have the potential to discriminate TNBC from other breast cancer groups, predict survival of the patients and augment the efficacy to anticancer treatment. However, this study raises many issues. First, miRNAs are not only specific for TNBC, but also for other breast cancer types. The identification of miRNAs playing a crucial role in TNBC need to be further elucidated. Second, the question whether we should try to enhance or inhibit miRNAs in cancer treatment is not straightforward since it might vary according to cell type, the stress signal and other circumstances. Third, the potential of miRNAs as therapeutic targets for TNBC is promising but at the same time still far off, the present published reports about miRNAs and TNBC lack functional or clinical supports. Although miRNAs has not been further explored for clinical application, our increased knowledge regarding the relationship between miRNAs and TNBC will provide technical mechanisms how the knowledge presented in the review could be utilized to assess the prognosis and enhance the effects of anticancer therapies for TNBC patients. Acknowledgements This study is supported by grants from National Natural Science Foundation of China (grant No. 81301891), Zhejiang Provincial Natural Science Foundation of China (grant No. LQ13H160008) and Zhengshu Medical Elite Scholarship Fund. Conflict of interest The authors declare no conflict of interest. References [1] T. Sorlie, C.M. Perou, R. Tibshirani, T. Aas, S. Geisler, H. Johnsen, et al., Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 10869–10874. [2] T. Sorlie, R. Tibshirani, J. Parker, T. Hastie, J.S. Marron, A. Nobel, et al., Repeated observation of breast tumor subtypes in independent gene expression data sets, Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 8418–8423. [3] C.M. Perou, T. Sørlie, M.B. Eisen, M. van de Rijn, S.S. Jeffrey, C.A. Rees, et al., Molecular portraits of human breast tumours, Nature 406 (2000) 747–752. [4] L. Carey, E. Winer, G. Viale, D. Cameron, L. Gianni, Triple-negative breast cancer: disease entity or title of convenience?, Nat. Rev. Clin. Oncol. 7 (2010) 683–692. [5] V.G. Abramson, B.D. Lehmann, T.J. Ballinger, J.A. Pietenpol, Subtyping of triple-negative breast cancer: implications for therapy, Cancer 121 (2015) 8–16. [6] N.C. Turner, J.S. Reis-Filho, Tackling the diversity of triple-negative breast cancer, Clin. Cancer Res. 19 (2013) 6380–6388. [7] R. Perez, A.V. Schally, I. Vidaurre, R. Rincon, N.L. Block, F.G. Rick, Antagonists of growth hormone-releasing hormone suppress in vivo tumor growth and gene expression in triple negative breast cancers, Oncotarget 3 (2012) 988–997.

11

[8] X. Chen, D. Iliopoulos, Q. Zhang, Q. Tang, M.B. Greenblatt, M. Hatziapostolou, et al., XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway, Nature 508 (2014) 103–107. [9] J. Crown, J. O’Shaughnessy, G. Gullo, Emerging targeted therapies in triplenegative breast cancer, Ann. Oncol. 23 (2012) vi56–vi65. [10] V. Ambros, The functions of animal microRNAs, Nature 431 (2004) 350–355. [11] J.C. Carrington, V. Ambros, Role of microRNAs in plant and animal development, Science 301 (2003) 336–338. [12] Y.W. Kong, D. Ferland-McCollough, T.J. Jackson, M. Bushell, MicroRNAs in cancer management, Lancet Oncol. 13 (2012) e249–e258. [13] G.A. Calin, C.M. Croce, MicroRNA signatures in human cancers, Nat. Rev. Cancer 6 (2006) 857–866. [14] H. Dvinge, A. Git, S. Gräf, M. Salmon-Divon, C. Curtis, A. Sottoriva, et al., The shaping and functional consequences of the microRNA landscape in breast cancer, Nature 497 (2013) 378–382. [15] L. Mulrane, R. Klinger, S.F. McGee, W.M. Gallagher, D.P. O’Connor, MicroRNAs: a new class of breast cancer biomarkers, Expert Rev. Mol. Diagn. 14 (2014) 347–363. [16] D. Serpico, L. Molino, S. Di Cosimo, MicroRNAs in breast cancer development and treatment, Cancer Treat. Rev. 40 (2014) 595–604. [17] M. Sochor, P. Basova, M. Pesta, N. Dusilkova, J. Bartos, P. Burda, et al., Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum, BMC Cancer 14 (2014) 448. [18] S. Zearo, E. Kim, Y. Zhu, J.T. Zhao, S.B. Sidhu, B.G. Robinson, et al., MicroRNA-484 is more highly expressed in serum of early breast cancer patients compared to healthy volunteers, BMC Cancer 14 (2014) 200. [19] L. Li, J. Luo, B. Wang, D. Wang, X. Xie, L. Yuan, et al., MicroRNA-124 targets flotillin-1 to regulate proliferation and migration in breast cancer, Mol. Cancer 12 (2013) 163. [20] S.H. Chan, W.C. Huang, J.W. Chang, K.J. Chang, W.H. Kuo, M.Y. Wang, et al., MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis, Oncogene 33 (2014) 4496–4507. [21] X.M. Ye, H.Y. Zhu, W.D. Bai, T. Wang, L. Wang, Y. Chen, et al., Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R, BMC Cancer 14 (2014) 134. [22] A. Paul, S. Gunewardena, S.R. Stecklein, B. Saha, N. Parelkar, M. Danley, et al., PKCλ/ι signaling promotes triple-negative breast cancer growth and metastasis, Cell Death Differ. 21 (2014) 1469–1481. [23] K.A. Avery-Kiejda, S.G. Braye, J.F. Forbes, S. RJ, The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer, BMC Cancer 14 (2014) 253. [24] J.Y. Li, S. Jia, W.H. Zhang, Y. Zhang, Y. Kang, P.S. Li, Differential distribution of microRNAs in breast cancer grouped by clinicopathological subtypes, Asian Pac. J. Cancer Prev. 14 (2013) 3197–3203. [25] R. Piva, D.A. Spandidos, R. Gambari, From microRNA functions to microRNA therapeutics: novel targets and novel drugs in breast cancer research and treatment (Review), Int. J. Oncol. 43 (2013) 985–994. [26] B. Humphries, Z. Wang, A.L. Oom, T. Fisher, D. Tan, Y. Cui, et al., MicroRNA-200b targets protein kinase Cα and suppresses triple-negative breast cancer metastasis, Carcinogenesis 35 (2014) 2254–2263. [27] E. Aydoğdu, A. Katchy, E. Tsouko, C.Y. Lin, L.A. Haldosén, L. Helguero, et al., MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer, Carcinogenesis 33 (2012) 1502–1511. [28] Y. Chen, Y. Sun, L. Chen, X. Xu, X. Zhang, B. Wang, et al., miRNA-200c increases the sensitivity of breast cancer cells to doxorubicin through the suppression of E-cadherin-mediated PTEN/Akt signaling, Mol. Med. Rep. 7 (2013) 1579–1584. [29] E.N. Howe, D.R. Cochrane, J.K. Richer, Targets of miR-200c mediate suppression of cell motility and anoikis resistance, Breast Cancer Res. 13 (2011) R45. [30] Y. Ren, X. Han, K. Yu, S. Sun, L. Zhen, Z. Li, et al., MicroRNA-200c downregulates XIAP expression to suppress proliferation and promote apoptosis of triplenegative breast cancer cells, Mol. Med. Rep. 10 (2014) 315–321. [31] E.N. Howe, D.R. Cochrane, D.M. Cittelly, J.K. Richer, miR-200c targets a NF-κB up-regulated TrkB/NTF3 autocrine signaling loop to enhance anoikis sensitivity in triple negative breast cancer, PLoS ONE 7 (2012) e49987. [32] C. Polytarchou, D. Iliopoulos, K. Struhl, An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state, Proc. Natl. Acad. Sci. U.S.A. 109 (2012) 14470–14475. [33] S. Valastyan, F. Reinhardt, N. Benaich, D. Calogrias, A.M. Szász, Z.C. Wang, et al., A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis, Cell 137 (2009) 1032–1046. [34] K. Augoff, B. McCue, E.F. Plow, K. Sossey-Alaoui, miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer, Mol. Cancer 11 (2012) 5. [35] T.C. Chang, E.A. Wentzel, O.A. Kent, K. Ramachandran, M. Mullendore, K.H. Lee, et al., Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis, Mol. Cell 26 (2007) 745–752. [36] Z. Feng, C. Zhang, R. Wu, W. Hu, Tumor suppressor p53 meets microRNAs, J. Mol. Cell Biol. 3 (2011) 44–50. [37] X. Deng, M. Cao, J. Zhang, K. Hu, Z. Yin, Z. Zhou, et al., Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer, Biomaterials 35 (2014) 4333–4344. [38] M. Mackiewicz, K. Huppi, J.J. Pitt, T.H. Dorsey, S. Ambs, N.J. Caplen, Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA, Breast Cancer Res. Treat. 130 (2011) 663– 679.

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X. Sui et al./Cancer Letters 361 (2015) 8–12

[39] K. Krishnan, A.L. Steptoe, H.C. Martin, D.R. Pattabiraman, K. Nones, N. Waddell, et al., miR-139-5p is a regulator of metastatic pathways in breast cancer, RNA 19 (2013) 1767–1780. [40] R.S. Wahdan-Alaswad, D.R. Cochrane, N.S. Spoelstra, E.N. Howe, S.M. Edgerton, S.M. Anderson, et al., Metformin-induced killing of triple-negative breast cancer cells is mediated by reduction in fatty acid synthase via miRNA-193b, Horm. Cancer 5 (2014) 374–389. [41] C. Wang, X. Zheng, C. Shen, Y. Shi, MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells, J. Exp. Clin. Cancer Res. 31 (2012) 58. [42] S. Savad, P. Mehdipour, M. Miryounesi, R. Shirkoohi, F. Fereidooni, F. Mansouri, et al., Expression analysis of MiR-21, MiR-205, and MiR-342 in breast cancer in Iran, Asian Pac. J. Cancer Prev. 13 (2012) 873–877. [43] C. Piovan, D. Palmieri, G. Di Leva, L. Braccioli, P. Casalini, G. Nuovo, et al., Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer, Mol. Oncol. 6 (2012) 458–472. [44] J. Wang, E. Tsouko, P. Jonsson, J. Bergh, J. Hartman, E. Aydogdu, et al., miR-206 inhibits cell migration through direct targeting of the actin-binding protein Coronin 1C in triple-negative breast cancer, Mol. Oncol. 8 (2014) 1690–1702. [45] A.J. Lowery, N. Miller, A. Devaney, R.E. McNeill, P.A. Davoren, C. Lemetre, et al., MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer, Breast Cancer Res. 11 (2009) R27. [46] Y. Zhao, C. Deng, W. Lu, J. Xiao, D. Ma, M. Guo, et al., let-7 microRNAs induce tamoxifen sensitivity by downregulation of estrogen receptor α signaling in breast cancer, Mol. Med. 17 (2011) 1233–1241. [47] E. Piskounova, C. Polytarchou, J.E. Thornton, R.J. LaPierre, C. Pothoulakis, J.P. Hagan, et al., Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms, Cell 147 (2011) 1066–1079. [48] T. Paranjape, H. Heneghan, R. Lindner, F.K. Keane, A. Hoffman, A. Hollestelle, et al., A 3’-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis, Lancet Oncol. 12 (2011) 377–386. [49] J.M. Gwak, H.J. Kim, E.J. Kim, Y.R. Chung, S. Yun, A.N. Seo, et al., MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer, Breast Cancer Res. Treat. 147 (2014) 39–49. [50] L. Chen, L.Y. Bourguignon, Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells, Mol. Cancer 13 (2014) 52. [51] G. Dong, X. Liang, D. Wang, H. Gao, L. Wang, L. Wang, et al., High expression of miR-21 in triple-negative breast cancers was correlated with a poor prognosis and promoted tumor cell in vitro proliferation, Med. Oncol. 31 (2014) 57. [52] X. Liu, X. Gu, L. Sun, A.B. Flowers, A.W. Rademaker, Y. Zhou, et al., Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triplenegative breast cancers: involvement of the RB-microRNA axis, BMC Cancer 14 (2014) 57. [53] J. Hu, J. Xu, Y. Wu, Q. Chen, W. Zheng, X. Lu, et al., Identification of microRNA-93 as a functional dysregulated miRNA in triple-negative breast cancer, Tumour Biol. 36 (2015) 251–258. [54] G. Eades, B. Wolfson, Y. Zhang, Q. Li, Y. Yao, Q. Zhou, lincRNA-RoR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6, Mol. Cancer Res. 13 (2015) 330–338. [55] A.I. Garcia, M. Buisson, P. Bertrand, R. Rimokh, E. Rouleau, B.S. Lopez, et al., Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers, EMBO Mol. Med. 3 (2011) 279–290. [56] W. Kong, L. He, E.J. Richards, S. Challa, C.X. Xu, J. Permuth-Wey, et al., Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer, Oncogene 33 (2014) 679–689. [57] J. Johansson, T. Berg, E. Kurzejamska, M.F. Pang, V. Tabor, M. Jansson, et al., MiR-155-mediated loss of C/EBPβ shifts the TGF-β response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer, Oncogene 32 (2013) 5614–5624.

[58] M.A. Taylor, K. Sossey-Alaoui, C.L. Thompson, D. Danielpour, W.P. Schiemann, TGF-β upregulates miR-181a expression to promote breast cancer metastasis, J. Clin. Invest. 123 (2013) 150–163. [59] A. Bisso, M. Faleschini, F. Zampa, V. Capaci, J. De Santa, L. Santarpia, et al., Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer, Cell Cycle 12 (2013) 1679–1687. [60] H. Liu, Y. Wang, X. Li, Y.J. Zhang, J. Li, Y.Q. Zheng, et al., Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1, Tumour Biol. 34 (2013) 1713–1722. [61] R. Nassirpour, P.P. Mehta, S.M. Baxi, M.J. Yin, miR-221 promotes tumorigenesis in human triple negative breast cancer cells, PLoS ONE 8 (2013) e62170. [62] M.T. Gyparaki, E.K. Basdra, A.G. Papavassiliou, MicroRNAs as regulatory elements in triple negative breast cancer, Cancer Lett. 354 (2014) 1–4. [63] T.A. Farazi, H.M. Horlings, J.J. Ten Hoeve, A. Mihailovic, H. Halfwerk, P. Morozov, et al., MicroRNA sequence and expression analysis in breast tumors by deep sequencing, Cancer Res. 71 (2011) 4443–4453. [64] C.M. Calvano Filho, D.C. Calvano-Mendes, K.C. Carvalho, G.A. Maciel, M.D. Ricci, A.P. Torres, et al., Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p, Tumour Biol. 35 (2014) 7733–7741. [65] P. Gasparini, L. Cascione, M. Fassan, F. Lovat, G. Guler, S. Balci, et al., MicroRNA expression profiling identifies a four microRNA signature as a novel diagnostic and prognostic biomarker in triple negative breast cancers, Oncotarget 5 (2014) 1174–1184. [66] S. Shen, Q. Sun, Z. Liang, X. Cui, X. Ren, H. Chen, et al., A prognostic model of triple-negative breast cancer based on miR-27b-3p and node status, PLoS ONE 9 (2014) e100664. [67] T. Toyama, N. Kondo, Y. Endo, H. Sugiura, N. Yoshimoto, M. Iwasa, et al., High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients, Jpn. J. Clin. Oncol. 42 (2012) 256–263. [68] T.A. Farazi, J.J. Ten Hoeve, M. Brown, A. Mihailovic, H.M. Horlings, M.J. van de Vijver, et al., Identification of distinct miRNA target regulation between breast cancer molecular subtypes using AGO2-PAR-CLIP and patient datasets, Genome Biol. 15 (2014) R9. [69] M. Svoboda, J. Sana, M. Redova, J. Navratil, M. Palacova, P. Fabian, et al., MiR-34b is associated with clinical outcome in triple-negative breast cancer patients, Diagn. Pathol. 7 (2012) 31. [70] K.A. Avery-Kiejda, S.G. Braye, A. Mathe, J.F. Forbes, R.J. Scott, Decreased expression of key tumour suppressor microRNAs is associated with lymph node metastases in triple negative breast cancer, BMC Cancer 14 (2014) 51. [71] A. Kolacinska, J. Morawiec, W. Fendler, B. Malachowska, Z. Morawiec, J. Szemraj, et al., Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report, Mol. Biol. Rep. 41 (2014) 2851–2857. [72] A. Sasaki, Y. Tsunoda, M. Tsuji, Y. Udaka, H. Oyamada, H. Tsuchiya, et al., Decreased miR-206 expression in BRCA1 wild-type triple-negative breast cancer cells after concomitant treatment with gemcitabine and a poly (ADP-ribose) polymerase-1 inhibitor, Anticancer Res. 34 (2014) 4893–4897. [73] C. Körner, I. Keklikoglou, C. Bender, A. Wörner, E. Münstermann, S. Wiemann, MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKC epsilon), J. Biol. Chem. 288 (2013) 8750– 8761. [74] M.Y. Wu, J. Fu, X. Xiao, J. Wu, R.C. Wu, MiR-34a regulates therapy resistance by targeting HDAC1 and HDAC7 in breast cancer, Cancer Lett. 354 (2014) 311–319. [75] M. Ouyang, Y. Li, S. Ye, J. Ma, L. Lu, W. Lv, et al., MicroRNA profiling implies new markers of chemoresistance of triple-negative breast cancer, PLoS ONE 9 (2014) e96228. [76] X. Tan, J. Peng, Y. Fu, S. An, K. Rezaei, S. Tabbara, et al., miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple negative breast cancer, Breast Cancer Res. 16 (2014) 435.

MicroRNAs-mediated cell fate in triple negative breast cancers.

MicroRNAs (miRNAs) are small non-coding RNAs that function as major modulators of posttranscriptional protein-coding gene expression in diverse biolog...
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