MicroRNA-9 Enhanced Cisplatin Sensitivity in Nonsmall Cell Lung Cancer Cells by Regulating Eukaryotic Translation Initiation Factor 5A2.

Qiaoling Pan,Guofeng Shao,Lebo Sun,Guodong Xu,Jie Song,Dawei Zheng,Huoshun Shi,Ni Li

doi:10.1155/2018/1769040

Qiaoling Pan, Guofeng Shao + Show 6 more

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https://doi.org/10.1155/2018/1769040

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Abstract

We determined the role of microRNA (miR)-9 in regulating cisplatin chemoresistance in nonsmall cell lung cancer (NSCLC) cells. miR-9 and eukaryotic translation initiation factor 5A2 (eIF5A2) levels were examined by reverse transcription–quantitative PCR. Cell Counting Kit-8 and the 5-ethynyl-2′-deoxyuridine (EdU) assay were used to determine the effects of miR-9 mimic or inhibitor on NSCLC cell proliferation and viability, respectively. Bioinformatics was used to analyze the relationship between miR-9 and eIF5A2. Flow cytometry was used to analyze the percentage of apoptotic cells. miR-9 mimic enhanced cisplatin sensitivity, while miR-9 inhibitor produced the opposite result. eIF5A2 was identified as a potential target of miR-9, where miR-9 regulated eIF5A2 expression at mRNA and protein level. miR-9 mimic decreased the expression of eIF5A2 mRNA and protein, while miR-9 inhibitor increased eIF5A2 expression. eIF5A2 knockdown resolved the effects of miR-9 mimic or inhibitor on cisplatin sensitivity. miR-9 may be a potential biomarker for enhancing cisplatin sensitivity by regulating eIF5A2 in NSCLC cells.

Highlights

Lung cancer is one of the most common malignancies and is a leading cause of cancer-related death worldwide [1]
A549 cells had the highest miR-9 expression among the three cell lines (Figure 1(b)). These results indicate that miR-9 expression correlates positively with cisplatin sensitivity in nonsmall cell lung cancer (NSCLC) cells
Western blotting demonstrated the interference efficiency of eukaryotic translation initiation factor 5A2 (eIF5A2) (Figure 4(a)). These results demonstrate that inhibiting eIF5A2 significantly increases the cisplatin sensitivity of NSCLC cells

Summary

Introduction

Lung cancer is one of the most common malignancies and is a leading cause of cancer-related death worldwide [1]. About 80% of lung cancer diagnosed is nonsmall cell lung cancer (NSCLC) [2]. Cisplatin is the most active chemotherapeutic agent against NSCLC; cisplatin resistance often occurs in clinical practice [3]. The process of cisplatin resistance is multifactorial and includes changes in drug accumulation and the apoptosis pathway, drug target interaction, and increased DNA repair [4]. The potential molecular mechanism of the development of cisplatin resistance remains unclear. There is a greatly urgent need to identify novel molecules to overcome cisplatin resistance in NSCLC

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