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Cited by 107MicroRNA in disease regulationOvarian cancer diagnosis and treatmentCancer-related molecular mechanisms research

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

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Báez-Vega, Perla M., Vargas, Ileabett M. Echevarría, Valiyeva, Fatma, Encarnación-Rosado, Joel, Roman, Adriana, Flores, Josean, Marcos-Martínez, María J., Vivas-Mejía, Pablo E.·2016·Oncotarget
DOI 10.18632/oncotarget.9216PMC PMC5095003
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Abstract

// Perla M. Báez-Vega 1 , Ileabett M. Echevarría Vargas 1, 2 , Fatma Valiyeva 1 , Joel Encarnación-Rosado 3 , Adriana Roman 3 , Josean Flores 4 , María J. Marcos-Martínez 5, 6 , Pablo E. Vivas-Mejía 1, 2 1 Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico 2 Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico 3 Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico 4 Ponce Health Sciences University, Ponce, Puerto Rico 5 Department of Pathology and Laboratory Medicine-University of Puerto Rico—School of Medicine, San Juan, Puerto Rico 6 Puerto Rico Medical Services Administration, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico Correspondence to: Pablo E. Vivas-Mejía, email: pablo.vivas@upr.edu 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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  • miR-21 is widely expressed in mammalian cells, is located on chromosome 17q23.2 in humans, and its upregulation is associated with various types of solid tumors.

    “miR-21 is a widespread expression of miRNA in mammalian cells located on chromosome 17q23.2 in humans, whose upregulation is associated with various types of solid tumors29–31.”

    From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [29]

    The Introduction (page unavailable) says miR-21-5p is overexpressed in most cancers, supporting the tumor-association part of the claim. It does not establish that miR-21 is widely expressed in mammalian cells or locate the human gene at chromosome 17q23.2; searches for those details found no supporting passage. (LLM, conf=0.88)

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References 37 · Cited by 107

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Authors
Báez-Vega, P. M., Vargas, I. M. E., Valiyeva, F., Encarnación-Rosado, J., Roman, A., Flores, J., Marcos-Martínez, M. J., & Vivas-Mejía, P. E.
Affiliations
  • Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico
  • University of Puerto Rico, Medical Sciences Campus (PR)
  • University of Puerto Rico at Río Piedras (PR)
  • Ponce Health Sciences University (PR)
ORCID
Encarnación-Rosado, Joel
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2016-05-07
Volume
7
Issue
24
Pages
36321-36337
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.9216
PMC
PMC5095003
OpenAlex
W2418616859
Cited by
107
References
37
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 14 · 2021: 15 · 2020: 22 · 2019: 10 · 2018: 12 · 2017: 13 · 2016: 3
FWCI
5.28
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (K22CA166226)
  • National Institute of General Medical Sciences (R25GM061838)
  • National Institute on Minority Health and Health Disparities (U54MD007587)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
miR-21-5p, ovarian cancer, cisplatin resistance, RBPMS, cell proliferation, cell invasion, miRNA inhibitors, chemoresistance, miRNA target genes, prostate cancer cells
MeSH terms
Adult, Aged, Antineoplastic Agents, Cisplatin, Female, Humans, Middle Aged, Neoplasm Invasiveness, Ovarian Neoplasms, Repressor Proteins, Gene Expression Regulation, Neoplastic, RNA-Binding Proteins, Cystadenocarcinoma, Serous, 3' Untranslated Regions, Guanine Nucleotide Exchange Factors, MicroRNAs, Cell Line, Tumor, Cell Proliferation, MCF-7 Cells

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