Abstract

MicroRNA (miRNAs) serve key roles in the progress of various types of cancer. The expression of miRNA (miR)-139-5p is downregulated in several types of tumor and has been recognized as a tumor suppressor. However, the role of miR-139-5p in non-small cell lung cancer (NSCLC) has not been investigated in detail. In the present study, it was demonstrated that miR-139-5p was significantly downregulated in NSCLC cells and tissues, and the overexpression of miR-139-5p in vitro induced apoptosis and significantly inhibited the viability and proliferation of A549 and H1299 cells. In addition, upregulation of miR-139-5p significantly inhibited the migration and invasion of A549 and H1299 cells. Hepatoma-derived growth factor (HDGF) was identified as a direct target of miR-139-5p. Rescue experiments demonstrated that the inhibitory function of miR-139-5p on cell viability, migration and invasion was partially mediated by suppressing HDGF expression. Furthermore, miR-139-5p exhibited efficient inhibition of tumor growth in a xenograft tumor mouse model of A549 cells. In summary, the results from the present study suggested that miR-139-5p may serve an important role in NSCLC by targeting HDGF and causing inhibition of cell viability and metastasis, as well as induction of apoptosis. miR-139-5p may also have the potential to serve as a therapeutic target for the treatment of NSCLC.

Highlights

  • Lung cancer is the main cause of cancer‐associated mortality worldwide, and ~85% of all lung cancer cases are classified as non‐small cell lung cancer (NSCLC) by histopathological analysis [1]

  • It was demonstrated that miR‐139‐5p expression was significantly downregulated in NSCLC, whereas overexpression of miR139‐5p significantly inhibited NSCLC cell viability and migration

  • These results suggested that downregulation of miR‐139‐5p expression may be associated with poor prognosis in patients with NSCLC

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Summary

Introduction

Lung cancer is the main cause of cancer‐associated mortality worldwide, and ~85% of all lung cancer cases are classified as non‐small cell lung cancer (NSCLC) by histopathological analysis [1]. The underlying mechanism of NSCLC development remains unknown. MicroRNAs (miRNAs) are small non‐coding RNAs that bind to the complimentary recognition sequences of the 3'‐untranslated region (3'‐UTR) of target mRNAs and lead to their degradation. This process suppresses the mRNA molecules from being translated into protein molecules [6,7,8]. MiRNAs serve as a regulator for the expression of a wide variety of target genes that are involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis [9,10,11,12]. The detailed role of miR‐139‐5p in NSCLC remains poorly understood

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