MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression

MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression

Author Maia, Beatriz de Melo Google Scholar
Rodrigues, Iara Santana Google Scholar
Akagi, Erica Mie Google Scholar
do Amaral, Nayra Soares Google Scholar
Ling, Hui Google Scholar
Monroig, Paloma Google Scholar
Soares, Fernando Augusto Google Scholar
Calin, George Adrian Google Scholar
Rocha, Rafael Malagoli Autor UNIFESP Google Scholar
Abstract MiR-223-5p has been previously mentioned to be associated with tumor metastasis in HPV negative vulvar carcinomas, such as in several other tumor types. In the present study, we hypothesized that this microRNA would be important in vulvar cancer carcinogenesis and progression. To investigate this, we artificially mimicked miR-223-5p expression in a cell line derived from lymph node metastasis of vulvar carcinoma (SW962) and performed in vitro assays. As results, lower cell proliferation (p < 0.01) and migration (p < 0.001) were observed when miR-223-5p was overexpressed. In contrast, increased invasive potential of these cells was verified (p < 0.004). In silico search indicated that miR-223-5p targets TP63, member of the TP53 family of proteins, largely described with importance in vulvar cancer. We experimentally demonstrated that this microRNA is capable to decrease levels of p63 at both mRNA and protein levels (p < 0.001, and p < 0.0001

respectively). Also, a significant inverse correlation was observed between miR-223-5p and p63 expressions in tumors from patients (p = 0.0365). Furthermore, low p63 protein expression was correlated with deeper tumor invasion (p = 0.0491) and lower patient overall survival (p = 0.0494). Our study points out miR-223-5p overexpression as a putative pathological mechanism of tumor invasion and a promising therapeutic target and highlights the importance of both miR-223-5p and p63 as prognostic factors in vulvar cancer. Also, it is plausible that the evaluation of p63 expression in vulvar cancer at the biopsy level may bring important contribution on prognostic establishment and in elaborating better surgical approaches for vulvar cancer patients.
Keywords vulvar cancer
microRNAs
cellular assays
hsa-miR-223-5p
TP63
Language English
Sponsor Sao Paulo Research Foundation (FAPESP) [2011/18065-6, 2013/04075-5]
NIH/NCI [CA135444]
Department of Defense Breast Cancer Idea Award
Developmental Research Award in Breast Cancer, Ovarian Cancer, Brain Cancer, Prostate Cancer, Multiple Myeloma, Leukemia [P50 CA100632]
Developmental Research Award in Head and Neck cancer [P50 CA097007]
SINF grant in colon cancer
Laura and John Arnold Foundation
RGK Foundation
Odyssey Program in the University of Texas MD Anderson Cancer Center
Grant number FAPESP:2011/18065-6
2013/04075-5
NIH/NCI:CA135444
BCRP:P50 CA100632
P50 CA097007]
Date 2016
Published in Oncotarget. Orchard Park, v. 7, n. 31, p. 49217-49231, 2016.
ISSN 1949-2553 (Sherpa/Romeo, impact factor)
Publisher Impact Journals Llc
Extent 49217-49231
Origin http://dx.doi.org/10.18632/oncotarget.10247
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000385422000031
URI http://repositorio.unifesp.br/handle/11600/51176

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