title: MiroRNA-127-3p targets XRCC3 to enhance the chemosensitivity of esophageal cancer cells to a novel phenanthroline-dione derivative.
abstract: 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.
authors: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Ni
authors: N
authors: Zhen
authors: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Qingyuan
authors: Q
authors: Yang
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, China.
authors: Kangdi
authors: K
authors: Zheng
authors: Department of Laboratory, Central Hospital of Panyu, Guangzhou, Guangdong, 511400, China.
authors: Zeping
authors: Z
authors: Han
authors: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors: Fenyong
authors: F
authors: Sun
authors: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, China. Electronic address: meiwenjie212@163.com.
authors: Wenjie
authors: W
authors: Mei
authors: Central Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated with Shanghai TCM University, Shanghai, 200071, China. Electronic address: yuyongchun2016@163.com.
authors: Yongchun
authors: Y
authors: Yu
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000473:pathology*; D059765:Homologous Recombination / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology*; D051135:Rad51 Recombinase / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C547276:MIRN127 microRNA, human; D035683:MicroRNAs; D010618:Phenanthrolines; C110901:X-ray repair cross complementing protein 3; D051135:Rad51 Recombinase
keywords: Chemosensitivity; Homologous recombination repair; Phenanthroline-dione derivative; XRCC3; microRNA-127-3p