title: miR-638 suppresses DNA damage repair by targeting SMC1A expression in terminally differentiated cells.
abstract: The reduction of DNA damage repair capacity in terminally differentiated cells may be involved in sensitivity to cancer chemotherapy drugs; however, the underlying molecular mechanism is still not fully understood. Herein, we evaluated the role of miR-638 in the regulation of DNA damage repair in terminally differentiated cells. Our results show that miR-638 expression was up-regulated during cellular terminal differentiation and involved in mediating DNA damage repair processes. Results from a luciferase reporting experiment show that structural maintenance of chromosomes (SMC)1A was a potential target of miR-638; this was verified by western blot assays during cell differentiation and DNA damage induction. Overexpression of miR-638 enhanced the sensitivity of cancer cells to cisplatin, thus reducing cell viability in response to chemotherapy drug treatment. Furthermore, miR-638 overexpression affected DNA damage repair processes by interfering with the recruitment of the DNA damage repair-related protein, γH2AX, to DNA break sites. These findings indicate that miR-638 might act as a sensitizer in cancer chemotherapy and accompany chemotherapy drugs to enhance chemotherapeutic efficacy and to improve the chance of recovery from cancer.
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: He
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Yunlan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Basic Medical Sciences, Wuhan University, 430071 Wuhan, P.R. China.
authors.forename: Guihong
authors.initials: G
authors.lastname: Sun
authors.affiliation: College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China.
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C572154:MIRN638 microRNA, human; D035683:MicroRNAs; D000098550:Structural Maintenance of Chromosome Protein 1; D002945:Cisplatin
keywords: DNA damage repair; SMC1A; cell differentiation; drug sensitivity; miR-638