MicroRNA-361-Mediated Inhibition of HSP90 Expression and EMT in Cervical Cancer Is Counteracted by Oncogenic lncRNA NEAT1.

Daozhi Xu,Ying Xiong,Hidemichi Watari,Yosuke Konno,Junming Yue,Yukiharu Todo,Noriko Kobayashi,Kei Ihira,Peixin Dong

doi:10.3390/cells9030632

Abstract

Epithelial-mesenchymal transition (EMT) is a key process contributing to cervical cancer (CC) metastasis, and microRNAs (miRNAs) modulate the expression of genes implicated in EMT. However, the accurate role of miR-361 in CC-associated EMT and the mechanisms underlying its function in CC remains largely unknown. The functional roles of miR-361 in CC cells were explored by a series of cell functional assays. Luciferase reporter assays were used to demonstrate the potential interaction between miR-361, HSP90, and long non-coding RNA (lncRNA) NEAT1. We detected a reduction of miR-361 expression in CC tissues compared with normal tissues, and miR-361 overexpression inhibited invasion and EMT phenotypes of CC cells by directly targeting a key EMT activator HSP90. Additionally, we detected significantly higher levels of HSP90 in CC tissues compared with normal tissues, and high expression of HSP90 predicted a poorer prognosis. We further identified NEAT1 as a significantly upregulated lncRNA in CC tissues and high expression of NEAT1 was associated with worse survival in CC patients. NEAT1 directly repressed miR-361 expression and played an oncogenic role in CC cell invasion and sphere formation. Conclusions: These results demonstrated that miR-361 directly targets HSP90 to inhibit the invasion and EMT features, and NEAT1 functions as an oncogenic lncRNA that suppresses miR-361 expression and induces EMT and sphere formation in CC cells, thus providing critical insights into the molecular pathways operating in this malignancy.

Highlights

Cervical cancer is one of the most common malignancies in women worldwide, with a 5-year relative survival rate of 16.5% for metastatic cervical cancer [1]
We discovered that NEAT1 functions as an oncogenic long non-coding RNA (lncRNA) that directly suppresses miR-361 expression and induces Epithelial-mesenchymal transition (EMT) and sphere formation in cervical cancer cells
Our results demonstrated that increased expression increased expression of ARF4, BSG, and HSP90 was significantly associated with shorter overall of ARF4, BSG, and HSP90 was significantly associated with shorter overall survival time in cervical survival time in cervical cancer patients (Figure 5), suggesting that these genes might act as oncogenes cancer patients (Figure 5), suggesting that these genes might act as oncogenes in cervical cancer, and in cervical cancer, and serve as potential biomarkers for predicting the prognosis of cervical cancer serve as potential biomarkers for predicting the prognosis of cervical cancer patients

Summary

Introduction

Cervical cancer is one of the most common malignancies in women worldwide, with a 5-year relative survival rate of 16.5% for metastatic cervical cancer [1]. Understanding the biology of metastatic cervical cancer cells will allow the development of novel therapeutic approaches aimed at improving the survival rates of patients with cervical cancer. Cancer metastasis begins with the process of epithelial-mesenchymal transition (EMT), which converts well-polarized epithelial cells to non-polarized mesenchymal cells that acquire motility and invasion properties and exhibit cancer stem cell-like properties [2]. EMT has been shown to play a role in the tumorigenic and metastatic process. EMT is triggered by EMT-activating transcription factors, such as SNAIL, TWIST, and ZEB families [2].

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Conclusion