MiR-375-3p inhibits the progression of laryngeal squamous cell carcinoma by targeting hepatocyte nuclear factor-1β.

Kunpeng Chang,Hua Cao,Zhenxing Wei

doi:10.3892/ol.2020.11941

Abstract

Laryngeal squamous cell carcinoma (LSCC) is one of the most frequently diagnosed head and neck cancers worldwide. Increasing evidence suggests that microRNAs (miRNAs/miRs) regulate the progression of tumorigenesis and the malignant behaviors of cancer cells. The aim of this study was to investigate the function and underlying mechanism of miR-375-3p in LSCC. The expression of miR-375-3p in LSCC tissues and cells was detected using reverse transcription-quantitative PCR. The effects of miR-375-3p on the malignant phenotype of LSCC cells was determined using the Cell Counting Kit-8 assay and flow cytometry. The targets of miR-375-3p were predicted using the miRDB database and confirmed by the luciferase reporter assay. The results of the present study demonstrated that miR-375-3p was downregulated in LSCC tissues and cell lines. Furthermore, overexpression of miR-375-3p significantly suppressed the proliferation and cell cycle progression of LSCC cells. Overexpression of miR-375-3p also increased LSCC cell apoptosis. Mechanistical analysis indicated that miR-375-3p bound the 3′-untranslated region of the hepatocyte nuclear factor 1β (HNF1β) and decreased its expression in LSCC cells. Consistent with the role of HNF1β in glucose metabolism, overexpression of miR-375-3p significantly inhibited glucose consumption and lactate production in LSCC cells. Transfection with HNF1β notably reversed the inhibitory effect of miR-375-3p on the proliferation of LSCC cells. Collectively, these results indicate the tumor suppressive role of miR-375-3p in LSCC via HNF1β, suggesting that miR-375-3p may serve as a potential target in the treatment of LSCC.

Highlights

Laryngeal squamous cell carcinoma (LSCC) is a common type of laryngeal cancer globally that frequently occurs in the larynx and accounts for 95% of laryngeal cancer cases in the recent decade [1,2,3]
Results miR‐375‐3p is downregulated in LSCC tissues and cell lines
RT‐qPCR analysis was performed to assess miR‐375‐3p expression in 50 paired LSCC tissues and matched adjacent normal tissues. miR‐375‐3p expression was significantly downregulated in LSCC tissues compared with adjacent normal tissues (Fig. 1A; ***P

Summary

Introduction

Laryngeal squamous cell carcinoma (LSCC) is a common type of laryngeal cancer globally that frequently occurs in the larynx and accounts for 95% of laryngeal cancer cases in the recent decade [1,2,3]. Chemotherapy, radiotherapy and immunotherapy have been used in the treat‐ ment of LSCC [4]. The mortality rate of patients with advanced LSCC remains high due to the limitations of these therapeutic strategies, such as chemo‐ and radio‐resis‐ tance [5]. The 5‐year overall survival rate of patients with LSCC is ~64% [5]. Some patients progress to advanced stages of the disease due to disease recurrence and metastasis [6].

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