GENES, CHROMOSOMES & CANCER 53:882 (2014)
Reply to Letter by Cristobal et al.
To the Editor:
We thank Cristobal and colleagues for their interest in and comments on our article (Liu et al., 2014b). We here address the questions raised. The first one is why we did not introduce all binding modes of microRNAs with their target mRNAs in the introduction section. The second one is that they observed a discrepancy in the data in Table 2 and suggested us to reanalyze the data. Last, they asked us to provide more information about the cohort of 92 CRC patients. It is well established that microRNAs induce mRNA degradation by binding to 30 -UTR. In recent years, some studies have demonstrated that microRNAs bind in the 50 -UTR and coding domain sequence (CDS) of mRNAs (Lytle et al., 2007; Zhou et al., 2009). However, microRNAs binding sites in the 30 -UTR is still the main direction of posttranscriptional gene regulation. Moreover, we found that miR-126 negatively regulate CXCR4 expression through binding to the 30 UTR of CXCR4 mRNA (Liu et al., 2014a). Thus, we consider that it is not essential to mention all biding modes of microRNAs with their target mRNAs. As regards the data in Table 2 (Liu et al., 2014b), it was pointed out that there was some discrepancy. It is a fact that there are 53 cases in stage III/IV and 40 patients with distant metastasis. Also, there are 40 patients in stage IV and 13 patients in stage III. Although a higher proportion of miR-126 downregulation was observed in patients without lymph node metastasis, there was no statistically significant difference between miR-126 expression and lymph node metastasis. Additionally, patients in stage IV may not necessarily have lymph node metastasis. Moreover, by following up the 92 CRC patients, we found that overall survival was associated with low miR-126 expression, not lymph node metastasis. To some extent, the apparent discrepancy may be due to an insufficient number of samples. Thus, a larger sample size may be needed in our further study.
C 2014 Wiley Periodicals, Inc. V
Regarding their last comment, further studies are needed to clarify the exact roles of miR-126 in CRC. First, to investigate the roles of miR-126 in CRC, in vivo experiments have been explored, such as establishing the metastatic mode of human CRC in nude mice. Second, we have investigated the relationship between miR-126 expression and metastasis, chemotherapy and radiation therapy in patients with CRC. We are eager to submit this report to evaluate the clinical significance of miR126 in CRC in the near future.
Yaling Liu Department of Gastroenterology Renmin Hospital of Wuhan University Wuhan, Hubei province, China Yu Zhou, Xiao Feng, Pengchun Yang, and Jingfang Yang Department of Gastroenterology The Affiliated Hospital of Guangdong Medical College Zhanjiang, Guangdong Province, China Ping An and Hesheng Luo* Department of Gastroenterology Renmin Hospital of Wuhan University Wuhan, Hubei province, China REFERENCES Liu Y, Zhou Y, Feng X, An P, Quan X, Wang H, Ye S, Yu C, He Y, Luo H. 2014a. MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways. Int J Oncol 44:203–210. Liu Y, Zhou Y, Feng X, Yang P, Yang J, An P, Wang H, Ye S, Yu C, He Y, Luo H. 2014b. Low expression of microRNA-126 is associated with poor prognosis in colorectal cancer. Genes Chromosomes Cancer 53:358–365. Lytle JR, Yario TA, Steitz JA. 2007. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 50 UTR as in the 30 UTR. Proc Natl Acad Sci USA 104:9667–9672. Zhou X, Duan X, Qian J, Li F. 2009. Abundant conserved microRNA target sites in the 50 -untranslated region and coding sequence. Genetica 137:159–164.
*Correspondence to: Hesheng Luo, Department of Gastroenterology, Renmin Hospital of Wuhan University. Number 238, Jiefang Road, Wuhan 430060, Hubei Province, China. E-mail: ([email protected]) Received 25 May 2014; Accepted 27 May 2014 DOI 10.1002/gcc.22193 Published online 10 June 2014 in Wiley Online Library (wileyonlinelibrary.com).
Reply to Letter by Cristobal et al.
To the Editor:
We thank Cristobal and colleagues for their interest in and comments on our article (Liu et al., 2014b). We here address the questions raised. The first one is why we did not introduce all binding modes of microRNAs with their target mRNAs in the introduction section. The second one is that they observed a discrepancy in the data in Table 2 and suggested us to reanalyze the data. Last, they asked us to provide more information about the cohort of 92 CRC patients. It is well established that microRNAs induce mRNA degradation by binding to 30 -UTR. In recent years, some studies have demonstrated that microRNAs bind in the 50 -UTR and coding domain sequence (CDS) of mRNAs (Lytle et al., 2007; Zhou et al., 2009). However, microRNAs binding sites in the 30 -UTR is still the main direction of posttranscriptional gene regulation. Moreover, we found that miR-126 negatively regulate CXCR4 expression through binding to the 30 UTR of CXCR4 mRNA (Liu et al., 2014a). Thus, we consider that it is not essential to mention all biding modes of microRNAs with their target mRNAs. As regards the data in Table 2 (Liu et al., 2014b), it was pointed out that there was some discrepancy. It is a fact that there are 53 cases in stage III/IV and 40 patients with distant metastasis. Also, there are 40 patients in stage IV and 13 patients in stage III. Although a higher proportion of miR-126 downregulation was observed in patients without lymph node metastasis, there was no statistically significant difference between miR-126 expression and lymph node metastasis. Additionally, patients in stage IV may not necessarily have lymph node metastasis. Moreover, by following up the 92 CRC patients, we found that overall survival was associated with low miR-126 expression, not lymph node metastasis. To some extent, the apparent discrepancy may be due to an insufficient number of samples. Thus, a larger sample size may be needed in our further study.
C 2014 Wiley Periodicals, Inc. V
Regarding their last comment, further studies are needed to clarify the exact roles of miR-126 in CRC. First, to investigate the roles of miR-126 in CRC, in vivo experiments have been explored, such as establishing the metastatic mode of human CRC in nude mice. Second, we have investigated the relationship between miR-126 expression and metastasis, chemotherapy and radiation therapy in patients with CRC. We are eager to submit this report to evaluate the clinical significance of miR126 in CRC in the near future.
Yaling Liu Department of Gastroenterology Renmin Hospital of Wuhan University Wuhan, Hubei province, China Yu Zhou, Xiao Feng, Pengchun Yang, and Jingfang Yang Department of Gastroenterology The Affiliated Hospital of Guangdong Medical College Zhanjiang, Guangdong Province, China Ping An and Hesheng Luo* Department of Gastroenterology Renmin Hospital of Wuhan University Wuhan, Hubei province, China REFERENCES Liu Y, Zhou Y, Feng X, An P, Quan X, Wang H, Ye S, Yu C, He Y, Luo H. 2014a. MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways. Int J Oncol 44:203–210. Liu Y, Zhou Y, Feng X, Yang P, Yang J, An P, Wang H, Ye S, Yu C, He Y, Luo H. 2014b. Low expression of microRNA-126 is associated with poor prognosis in colorectal cancer. Genes Chromosomes Cancer 53:358–365. Lytle JR, Yario TA, Steitz JA. 2007. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 50 UTR as in the 30 UTR. Proc Natl Acad Sci USA 104:9667–9672. Zhou X, Duan X, Qian J, Li F. 2009. Abundant conserved microRNA target sites in the 50 -untranslated region and coding sequence. Genetica 137:159–164.
*Correspondence to: Hesheng Luo, Department of Gastroenterology, Renmin Hospital of Wuhan University. Number 238, Jiefang Road, Wuhan 430060, Hubei Province, China. E-mail: ([email protected]) Received 25 May 2014; Accepted 27 May 2014 DOI 10.1002/gcc.22193 Published online 10 June 2014 in Wiley Online Library (wileyonlinelibrary.com).
