Oncotarget

Research Papers:

Targeting miR-21-3p inhibits proliferation and invasion of ovarian cancer cells

Perla M. Báez-Vega, Ileabett M. Echevarría Vargas, Fatma Valiyeva, Joel Encarnación-Rosado, Adriana Roman, Josean Flores, María J. Marcos-Martínez and Pablo E. Vivas-Mejía _

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Oncotarget. 2016; 7:36321-36337. https://doi.org/10.18632/oncotarget.9216

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Abstract

Perla M. Báez-Vega1, Ileabett M. Echevarría Vargas1,2, Fatma Valiyeva1, Joel Encarnación-Rosado3, Adriana Roman3, Josean Flores4, María J. Marcos-Martínez5,6, Pablo E. Vivas-Mejía1,2

1Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico

2Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico

3Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico

4Ponce Health Sciences University, Ponce, Puerto Rico

5Department of Pathology and Laboratory Medicine-University of Puerto Rico—School of Medicine, San Juan, Puerto Rico

6Puerto Rico Medical Services Administration, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico

Correspondence to:

Pablo E. Vivas-Mejía, email: [email protected]

Keywords: ovarian cancer, microRNAs, miR-21-3p, cisplatin, RBPMS

Received: September 01, 2015     Accepted: April 18, 2016     Published: May 07, 2016

ABSTRACT

MicroRNA-21 is overexpressed in most cancers and has been implicated in tumorigenesis. Accumulating evidence supports a central role for the miR-21 guide strand (miR-21-5p) in ovarian cancer initiation, progression, and chemoresistance. However, there is limited information regarding the biological role of the miR-21 passenger strand (miR-21-3p) in ovarian cancer cells. The aim of this study was to investigate the role of miR-21-3p and its target genes in cisplatin-resistant ovarian cancer cells. Expression profiling of miR-21-5p and miR-21-3p was performed in a panel of cancer cells by qPCR. Colony formation and invasion assays were carried out on ovarian and prostate cancer cells transfected with miR-21-5p and miR-21-3p inhibitors. Dual luciferase reporter assays were used to identify the miR-21-3p target genes in ovarian cancer cells. Our results show that miR-21-5p had higher expression levels compared to miR-21-3p on a panel of cancer cells. Moreover, inhibition of miR-21-5p or miR-21-3p resulted in a significant decrease in ovarian and prostate cancer cell proliferation and invasion. Luciferase reporter assays identify RNA Binding Protein with Multiple Splicing (RBPMS), Regulator of Chromosome Condensation and POZ Domain Containing Protein 1 (RCBTB1), and Zinc Finger protein 608 (ZNF608) as miR-21-3p target genes. SiRNA-induced RBPMS silencing reduced the sensitivity of ovarian cancer cells to cisplatin treatment. Immunohistochemical analyses of serous ovarian cancer patient samples suggest a significant decrease of RBMPS levels when compared to normal ovarian epithelium. Taken together, the data generated in this study suggests a functional role for miR-21-3p in ovarian cancer and other solid tumors.


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