MiroRNA-127-3p targets XRCC3 to enhance the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivative

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• 作者：Ni Zhen^a ; ¹ ; Qingyuan Yang^a ; ¹ ; Kangdi Zheng^b ; Zeping Han^c ; Fenyong Sun^a ; Wenjie Mei^b ; ^{meiwenjie212@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yongchun Yu^d ; ^{yuyongchun2016@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：microRNA-127-3p ; XRCC3 ; Homologous recombination repair ; Chemosensitivity ; Phenanthroline-dione derivative
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：79
• 期：Complete
• 页码：158-167
• 全文大小：4223 K

文摘

MicroRNAs are small non-coding RNAs with 18–22 nucleotides in length and have been proposed to function in various biological processes by targeting genes for post-transcriptional degradation via their 3′ untranslated region. Moreover, they have been suggested to improve the chemosensitivity in a panel of tumors. However, the biological functions of microRNA-127-3p in esophageal carcinogenesis are still enigmatic. Thus, in the study, we firstly analyzed the roles of microRNA-127-3p in regulating the growth of esophageal cancer cells both in vitro and in vivo. Afterwards, using the microRNA-targeted gene prediction software and the dual-luciferase reporter assays, we confirmed that microRNA-127-3p specifically reduced the expression of X-ray repair complementing defective repair in Chinese hamster cells 3, one of RAD51 recombinase paralogs, at both mRNA and protein levels. Furthermore, using the homologous recombination repair and non-homologous end joining repair reporter systems, we found that microRNA-127-3p specifically compromised the homologous recombination repair and significantly increased DNA double strand breaks in cells. Besides, it statistically increased the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivative in vivo by mechanistically impairing the recruitment of RAD51 to the damage sites. In summary, our findings not only suggest that microRNA-127-3p can be used as a predictor for evaluating the development of esophageal carcinoma, but also show that it can be used to increase the chemosensitivity of esophageal cancer patients to the phenanthroline-dione derivative, which might be a potential anticancer candidate in the future.