TY - JOUR
T1 - MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression
AU - Maia, Beatriz de Melo
AU - Rodrigues, Iara Santana
AU - Akagi, Erica Mie
AU - do Amaral, Nayra Soares
AU - Ling, Hui
AU - Monroig, Paloma
AU - Soares, Fernando Augusto
AU - Calin, George Adrian
AU - Rocha, Rafael Malagoli
N1 - Funding Information:
Beatriz Maia received scholarship support provided by The São Paulo Research Foundation (FAPESP) (Process #2011/18065-6 and BEPE Process#2013/04075-5). George Calin is The Alan M. Gewirtz Leukemia and Lymphoma Society Scholar. He is supported as a fellow at The University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation. Work in Calin's laboratory is supported, in part, by the NIH/NCI (CA135444), a Department of Defense Breast Cancer Idea Award, Developmental Research Awards in Breast Cancer, Ovarian Cancer, Brain Cancer, Prostate Cancer, Multiple Myeloma, Leukemia (P50 CA100632), and Head and Neck cancer (P50 CA097007) SPOREs, a SINF MDACC_DKFZ grant in CLL, a SINF grant in colon cancer, the Laura and John Arnold Foundation, the RGK Foundation, and the Estate of CG Johnson, Jr. Hui Ling is an Odyssey Fellow, and his work was supported, in part, by the Odyssey Program in the University of Texas MD Anderson Cancer Center.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Cellular assays
KW - Hsa-miR-223-5p
KW - MicroRNAs
KW - TP63
KW - Vulvar cancer
UR - http://www.scopus.com/inward/record.url?scp=84981313529&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84981313529&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.10247
DO - 10.18632/oncotarget.10247
M3 - Article
C2 - 27359057
AN - SCOPUS:84981313529
SN - 1949-2553
VL - 7
SP - 49217
EP - 49231
JO - Oncotarget
JF - Oncotarget
IS - 31
ER -