MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression.
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.
['de Melo Maia|Beatriz|B|', 'Rodrigues|Iara Santana|IS|', 'Akagi|Erica Mie|EM|', 'Soares do Amaral|Nayra|N|', 'Ling|Hui|H|', 'Monroig|Paloma|P|', 'Soares|Fernando Augusto|FA|', 'Calin|George Adrian|GA|', 'Rocha|Rafael Malagoli|RM|']
D001706:Biopsy D063646:Carcinogenesis D002277:Carcinoma D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D018450:Disease Progression D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D006801:Humans D035683:MicroRNAs D009361:Neoplasm Invasiveness D009362:Neoplasm Metastasis D009857:Oncogenes D011379:Prognosis D012333:RNA, Messenger D014157:Transcription Factors D016896:Treatment Outcome D025521:Tumor Suppressor Proteins D014846:Vulvar Neoplasms D014945:Wound Healing
TP63 microRNAs vulvar cancer cellular assays hsa-miR-223-5p