MicroRNA-134-3p is a novel potential inhibitor of human ovarian cancer stem cells by targeting RAB27A

Cui Chang; Te Liu; Yongyi Huang; Wenxing Qin; Hongtu Yang; Juan Chen

doi:10.1016/j.gene.2016.12.030

MicroRNA-134-3p is a novel potential inhibitor of human ovarian cancer stem cells by targeting RAB27A

Gene. 2017 Mar 20:605:99-107. doi: 10.1016/j.gene.2016.12.030. Epub 2016 Dec 31.

Authors

Cui Chang¹, Te Liu², Yongyi Huang³, Wenxing Qin⁴, Hongtu Yang⁵, Juan Chen⁶

Affiliations

¹ Department of Pharmaceutical Science, Shenzhen People's Hospital, Second Clinical College, Jinan University, Shenzhen 518020, China.
² Department of Pathology, Yale University School of Medicine, New Haven 06520, USA; Shanghai Tenth People's Hospital, Medical School, Tongji University, Shanghai 200072, China. Electronic address: te.liu@yale.edu.
³ Laboratoire PROTEE, Bâtiment R, Université du Sud Toulon-Var, 83957 La Garde Cedex, France.
⁴ Department of Medical Oncology, Shanghai Changzheng Hospital, Affiliated to The Second Military Medical University, Shanghai 200070, China.
⁵ Department of Pharmaceutical Science, Shenzhen People's Hospital, Second Clinical College, Jinan University, Shenzhen 518020, China. Electronic address: yht2113@126.com.
⁶ Gongli Hospital Affiliated to the Second Military Medicical University in Pudong New Area of Shanghai City, Shanghai 200135, China. Electronic address: 406526258@qq.com.

PMID: 28043921
DOI: 10.1016/j.gene.2016.12.030

Abstract

The cluster of microRNAs (miRNAs) in the DLK1-DIO3 genomic imprinted region contains several miRNAs that have a significant regulatory role in tumor proliferation and invasion. One of these miRNAs is miR-134-3p, and its expression changes significantly in human ovarian cancer stem cells (OCSCs) and in CD44-/CD133- ovarian cancer. The results of a luciferase assay showed that miR-134-3p silenced RAB27A by binding to the 3'-UTR of RAB27A mRNA. Overexpression of miR-134-3p in human OCSCs can not only inhibit the expression of RAB27A but also can effectively downregulate the expression of some tumor proliferation and invasion genes. Overexpression of miR-134-3p can not only inhibit the in vitro proliferation and cell cycle progression of human OCSCs but also can decrease the tumorigenicity in nude mice.

Keywords: DLK1-DIO3 microRNA cluster; MicroRNA-134-3p (miR-134-3p); Ovarian cancer stem cells (OCSCs); RAB27A.

MeSH terms

Adenocarcinoma, Clear Cell / genetics*
Adenocarcinoma, Clear Cell / metabolism
Adenocarcinoma, Clear Cell / pathology
Adult
Aged
Animals
Base Sequence
Binding Sites
Cell Proliferation
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Genes, Reporter
Humans
Luciferases / genetics
Luciferases / metabolism
Mice
Mice, Nude
MicroRNAs / genetics*
MicroRNAs / metabolism
Middle Aged
Neoplasm Invasiveness
Neoplasm Staging
Neoplasm Transplantation
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Primary Cell Culture
Signal Transduction
rab GTP-Binding Proteins / genetics*
rab GTP-Binding Proteins / metabolism
rab27 GTP-Binding Proteins

Substances

MIRN134 microRNA, human
MicroRNAs
rab27 GTP-Binding Proteins
Luciferases
RAB27A protein, human
rab GTP-Binding Proteins