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. (C) 2016 Elsevier Ltd. All rights reserved.
[1]Tongji Univ, Dept Clin Lab Med, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China.
[2]Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Guangdong, Peoples R China.
[3]Cent Hosp Panyu, Dept Lab, Guangzhou 511400, Guangdong, Peoples R China.
[4]Shanghai TCM Univ, Cent Lab, Shanghai Municipal Hosp Tradit Chinese Med, Shanghai 200071, Peoples R China.
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