miR-30a can inhibit DNA replication by targeting RPA1 thus slowing cancer cell proliferation

Zhenyou Zou; Mengjie Ni; Jing Zhang; Yongfeng Chen; Hongyu Ma; Shihan Qian; Longhua Tang; Jiamei Tang; Hailun Yao; Chengbin Zhao; Xiongwen Lu; Hongyang Sun; Jue Qian; Xiaoting Mao; Xulin Lu; Qun Liu; Juping Zen; Hanbing Wu; Zhaosheng Bao; Shudan Lin; Hongyu Sheng; Yunlong Li; Yong Liang; Zhiqiang Chen; Dan Zong

doi:10.1042/BCJ20160177

miR-30a can inhibit DNA replication by targeting RPA1 thus slowing cancer cell proliferation

Biochem J. 2016 Jul 15;473(14):2131-9. doi: 10.1042/BCJ20160177. Epub 2016 May 17.

Authors

Zhenyou Zou¹, Mengjie Ni², Jing Zhang³, Yongfeng Chen², Hongyu Ma⁴, Shihan Qian², Longhua Tang², Jiamei Tang², Hailun Yao², Chengbin Zhao², Xiongwen Lu², Hongyang Sun², Jue Qian², Xiaoting Mao², Xulin Lu², Qun Liu², Juping Zen², Hanbing Wu², Zhaosheng Bao², Shudan Lin², Hongyu Sheng², Yunlong Li², Yong Liang², Zhiqiang Chen², Dan Zong²

Affiliations

¹ Tumor Institute of Taizhou University, Taizhou, ZJ 318000, China Life Sciences School of Nanjing University, Nanjing, JS 210093, China Biochemical Department of Purdue University, West Lafayette, IN 47906, U.S.A. sokuren@163.com.
² Tumor Institute of Taizhou University, Taizhou, ZJ 318000, China.
³ Tumor Institute of Taizhou University, Taizhou, ZJ 318000, China Life Sciences School of Nanjing University, Nanjing, JS 210093, China.
⁴ Plant Protecting School of Nanjing Agricultural University, Nanjing, JS 210093, China.

PMID: 27208176
DOI: 10.1042/BCJ20160177

Abstract

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development.

Keywords: DNA replication; RPA1; S-phase checkpoint; cell cycle arrest; miR-30a.

MeSH terms

Apoptosis / genetics
Apoptosis / physiology
Ataxia Telangiectasia Mutated Proteins / genetics
Ataxia Telangiectasia Mutated Proteins / metabolism
Cell Cycle / genetics
Cell Cycle / physiology
Cell Line, Tumor
Cell Proliferation / genetics
Cell Proliferation / physiology*
Cellular Senescence / genetics
Cellular Senescence / physiology
Checkpoint Kinase 2 / genetics
Checkpoint Kinase 2 / metabolism
Comet Assay
DNA Replication / genetics
DNA Replication / physiology*
Histones / metabolism
Humans
Immunohistochemistry
MicroRNAs / genetics
MicroRNAs / metabolism
MicroRNAs / physiology*
RNA Interference / physiology
Replication Protein A / genetics
Replication Protein A / metabolism*

Substances

H2AX protein, human
Histones
MIRN30b microRNA, human
MicroRNAs
RPA1 protein, human
Replication Protein A
Checkpoint Kinase 2
Ataxia Telangiectasia Mutated Proteins