Author |
Maia, Beatriz de Melo
![]() Rodrigues, Iara Santana ![]() Akagi, Erica Mie ![]() do Amaral, Nayra Soares ![]() Ling, Hui ![]() Monroig, Paloma ![]() Soares, Fernando Augusto ![]() Calin, George Adrian ![]() Rocha, Rafael Malagoli ![]() ![]() |
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 |
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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 |
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Access rights | Open access ![]() |
Type | Article |
Web of Science ID | WOS:000385422000031 |
URI | http://repositorio.unifesp.br/handle/11600/51176 |
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