Dados do Trabalho

Título

MicroRNA-205-5p Modulation and Its Effects on Cervical Cancer Cell Behavior: Insights into Progression Mechanisms

Introdução

MicroRNAs (miRNAs) function to modulate the pathophysiologic mechanism in cancer, through activation and inactivation of important signaling pathways, which might offer a new approach for the diagnosis, prognosis, and treatment of cervical cancer patients in the future. Recent studies have shown that miR-205-5p could be used as good biomarkers for CIN 3 lesions. In addition, this miRNA may be involved in crucial stages of cervical cancer progression.

Objetivo

To evaluate in vitro the functional role of miR-205-5p in the proliferation, migration, and invasion of cervical cancer cell lines.

Métodos

The miR-205-5p expression was evaluated by quantitative PCR (qPCR) in a panel of cervical cancer cell lines in comparison with non-tumorigenic epithelial cell line HaCaT. We transfected cervical cancer cells (CaSki, C-4 I, and HCB-514) with negative control (scramble) or LNA miR-205-5p inhibitor (anti-miR-205-5p), and the capacity of proliferation, migration, and invasion was evaluated. Characterization of the transcriptional profile between cells that received inhibition of miRNAs versus the negative control was performed using the nCounter PanCancer Progression panel (NanoString Technologies). Subsequently, in silico analyzes were performed to validate possible targets miR-205-5p.

Resultados

We identified that miR-205-5p was overexpressed in CaSki, C4-I, and HCB-514 cells. Functionally, it was shown that cells transfected with anti-miR-205-5p significantly reduced the proliferation, migration, and invasion of CaSki, C4-I, and HCB-514 cells when compared to cells transfected with the negative control. Gene expression profile analysis identified three overexpressed genes (MGP, MMRN2, and FXYD6) after inhibition of miR-205-5p expression. In silico analysis revealed that the FXYD6 gene is predicted to be a target of miR-205-5p. This finding implies that miR-205-5p might regulate the expression of FXYD6, which could influence ion transport pathways and activation of HOX genes during tumor differentiation. Therefore, the interaction between miR-205-5p and FXYD6 appears to be part of a regulatory axis that affects ion transport pathways and the activation of HOX genes, which are crucial for cellular differentiation. This suggests a potential mechanism by which miR-205-5p contributes to cervical cancer progression.

Conclusões

This study provides valuable insights into the functional role of miR-205-5p in cervical cancer progression and its potential implications as a biomarker for identifying and monitoring the disease. The findings suggest a regulatory axis involving miR-205-5p and FXYD6 during cervical cancer progression.

Palavras-chave

cervical cancer, progression, microRNAs

Financiador do resumo

The present study was funded by FAPESP (grant no. 2016/15831-3), the Research Incentive Program of Barretos Cancer Hospital (PAIP) and PRONON. The present study was also funded by the São Paulo Research Foundation (FAPESP; grant no. 2018/19476-9) and this research was funded by the Brazilian Ministry of Health supported by PRONON/MS (NUP-25000.023997.2018/34) entitled: ‘Identificação de biomarcadores para screening e detecção precoce de tumores no contexto do Sistema Único de Saúde (SUS).’ RMR and MMCM are recipients of a CNPq Productivity fellowship.