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Int. J. Mol. Sci. 2016, 17(8), 1351; doi:10.3390/ijms17081351

MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2

1
Department of Pathology, Nara Medical University School of Medicine, Nara 634-8521, Japan
2
Department of Diagnostic Pathology, Nara City Hospital, Nara 630-8305, Japan
3
Department of Central Clinical Laboratory, Nara Medical University Hospital, Nara 634-8521, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Y-h. Taguchi and Kumiko UI-TEI
Received: 23 July 2016 / Revised: 11 August 2016 / Accepted: 12 August 2016 / Published: 18 August 2016
(This article belongs to the Special Issue microRNA Regulation 2017)
View Full-Text   |   Download PDF [4901 KB, uploaded 18 August 2016]   |  

Abstract

Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3′-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects. View Full-Text
Keywords: cervical cancer; human papillomavirus; miR-331-3p; neuropilin 2; E6/E7 mRNA; keratinocyte differentiation cervical cancer; human papillomavirus; miR-331-3p; neuropilin 2; E6/E7 mRNA; keratinocyte differentiation
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MDPI and ACS Style

Fujii, T.; Shimada, K.; Asano, A.; Tatsumi, Y.; Yamaguchi, N.; Yamazaki, M.; Konishi, N. MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2. Int. J. Mol. Sci. 2016, 17, 1351.

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