title: MiR-223-5p works as an oncomiR in vulvar carcinoma by TP63 suppression.
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.
authors.affiliation: Molecular Morphology Laboratory, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.|Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Melo Maia
authors.affiliation: Molecular Morphology Laboratory, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Iara Santana
authors.initials: IS
authors.lastname: Rodrigues
authors.affiliation: Molecular Morphology Laboratory, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Erica Mie
authors.initials: EM
authors.lastname: Akagi
authors.affiliation: Molecular Morphology Laboratory, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Nayra
authors.initials: N
authors.lastname: Soares do Amaral
authors.affiliation: Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.affiliation: Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Paloma
authors.initials: P
authors.lastname: Monroig
authors.affiliation: Molecular Morphology Laboratory, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.|The Center for RNA Interference and Non-Coding RNAs, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: George Adrian
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Gynecology Laboratory, Gynecologic Department Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
mesh_terms: D001706:Biopsy; D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009857:Oncogenes; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C525067:MIR223, human; C115051:TP63 protein, human
keywords: TP63; cellular assays; hsa-miR-223-5p; microRNAs; vulvar cancer