title: Targeting miR-21-3p inhibits proliferation and invasion of ovarian cancer cells.
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.
authors.affiliation: Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Perla M
authors.initials: PM
authors.lastname: Báez-Vega
authors.affiliation: Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.|Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Ileabett M
authors.initials: IM
authors.lastname: Echevarría Vargas
authors.affiliation: Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Fatma
authors.initials: F
authors.lastname: Valiyeva
authors.affiliation: Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
authors.forename: Joel
authors.initials: J
authors.lastname: Encarnación-Rosado
authors.affiliation: Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Roman
authors.affiliation: Ponce Health Sciences University, Ponce, Puerto Rico.
authors.forename: Josean
authors.initials: J
authors.lastname: Flores
authors.affiliation: Department of Pathology and Laboratory Medicine-University of Puerto Rico-School of Medicine, San Juan, Puerto Rico.|Puerto Rico Medical Services Administration, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: María J
authors.initials: MJ
authors.lastname: Marcos-Martínez
authors.affiliation: Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.|Department of Biochemistry, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Vivas-Mejía
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C486398:BCL6B protein, human; D020662:Guanine Nucleotide Exchange Factors; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C101827:RBPMS protein, human; C482643:RCBTB1 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D002945:Cisplatin
keywords: RBPMS; cisplatin; miR-21-3p; microRNAs; ovarian cancer