LncRNA SNHG14 regulates the DDP-resistance of non-small cell lung cancer cell through miR-133a/HOXB13 pathway

Li Xu,Fang Xu,Bo-Lin Chen,Min Yang,Jia Li,Yan Xu

doi:10.1186/s12890-020-01276-7

Li Xu, Fang Xu + Show 4 more

Open Access

https://doi.org/10.1186/s12890-020-01276-7

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Abstract

BackgroundRecently, long non-coding RNAs (lncRNAs) have been reported to be involved in regulating chemo-resistance of NSCLC, however, the role of lncRNA SNHG14 in the DDP-resistance of NSCLC remains unexplored.MethodsRelative expression of SNHG14, HOXB13 and miR-133a in DDP-resistant A549 (A549/DDP) cell and its parental cell A549 were measured using qRT-PCR. Cell proliferation viability of indicated A549/DDP cell was estimated via CCK-8 and colony formation experiments. Cell cycle and apoptosis were analyzed through flow cytometry. Expression of apoptosis-related protein and HOXB13 were detected via western blot. The interaction among SNHG14, HOXB13 and miR-133a was predicted by bioinformatics and validated by dual-luciferase reporter assay.ResultsLncRNA SNHG14 and HOXB13 were upregulated while miR-133a was downregulated in A549/DDP cell line compared to A549 cell line. SNHG14 knockdown or miR-133a overexpression was demonstrated to increase the DDP-sensitivity of A549/DDP cells. SNHG14 was revealed to compete with HOXB13 for miR-133a binding in A549/DDP cells. Inhibition of miR-133a in A549 cells could reverse the promotive effects of SNHG14 knockdown on DDP-sensitivity, as well as the inhibitory effects on HOXB13 expression. HOXB13 overexpression was revealed to abolish the enhanced effects of miR-133a on the sensitivity of A549/DDP cell to DDP.ConclusionOur findings demonstrated that SNHG14 was involved in the development of DDP-resistance of A549/DDP cells through miR-133a/HOXB13 axis, which may present a path to novel therapeutic stratagems for DDP resistance of NSCLC.

Highlights

Long non-coding RNAs have been reported to be involved in regulating chemoresistance of Non-small cell lung cancer (NSCLC), the role of long non-coding RNAs (lncRNAs) LncRNAsmall nucleolar RNA host gene 14 (SNHG14) in the DDP-resistance of NSCLC remains unexplored
LncRNA SNHG14 and Homeobox B13 (HOXB13) were highly expressed, while miR-133a was lowly expressed in DDP-resistant NSCLC cell To investigate whether lncRNA SNHG14, HOXB13 and miR-133a play roles in the chemo-resistance of NSCLC, we firstly examined their expression in parental NSCLC cell (A549) and DDP-resistant NSCLC cell (A549/DDP) using Quantitative real-time PCR (qRT-PCR)
As results indicated that lncRNA SNHG14 and HOXB13 were remarkably increased, while miR-133a was significantly decreased in A549/ DDP cells compared with A549 cells (Fig. 1a)

Summary

Introduction

Long non-coding RNAs (lncRNAs) have been reported to be involved in regulating chemoresistance of NSCLC, the role of lncRNA SNHG14 in the DDP-resistance of NSCLC remains unexplored. The high mortality of lung cancer is largely due to the common diagnosis at advanced stages that impedes the curative treatment [2]. Xu et al BMC Pulmonary Medicine (2020) 20:266 the tumor is inoperable. These are the reasons why the five-year survival rate of NSCLC patients is less than 20% [3]. Cisplatin (DDP) is used as a first-line agent in the treatment of those postoperative or inoperable NSCLC patients [4]. The cancer-related death was previously demonstrated to decrease in the NSCLC patients who received DDP chemotherapy for 5 years compared to those untreated patients [5]. DDP resistance is considered to be one of the most important impediments to the therapy of NSCLC patients

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