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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2019

01-05-2019 | NSCLC | Original Article

The PVT1/miR-216b/Beclin-1 regulates cisplatin sensitivity of NSCLC cells via modulating autophagy and apoptosis

Authors: Liangfeng Chen, Xiaobing Han, Zhongzhou Hu, Liangxin Chen

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2019

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Abstract

Purpose

The efficacy of cisplatin-based chemotherapy remains an open question for chemo-resistance in non-small cell lung cancer (NSCLC). This study aimed to explore the role and mechanism of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) in cisplatin sensitivity of NSCLC.

Methods

Paired tumor and adjacent tissues were collected from forty patients with NSCLC. The clinical value of PVT1 was investigated according to clinicopathological parameters of patients. Cisplatin-sensitive or -resistant cells (A549 or A549/DDP) were used for in vitro experiments. Cell viability, apoptosis, autophagy and animal experiments were conducted to investigate cisplatin sensitivity. The expressions of PVT1, microRNA-216b (miR-216b) and apoptosis- or autophagy-related proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot assay, respectively. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to probe the interaction between miR-216b and PVT1 or Beclin-1.

Results

PVT1 was highly expressed and associated with poor prognosis of NSCLC patients (*P < 0.05). PVT1 knockdown enhanced cisplatin-induced viability inhibition and apoptosis induction in A549/DDP cells, but addition of PVT1 caused an opposite effect in A549 cells (*P < 0.05, #P < 0.05). Moreover, accumulation of PVT1 facilitated autophagy of NSCLC cells and tumor growth in vivo (*P < 0.05, #P < 0.05). In addition, miR-216b interacted with PVT1 or Beclin-1. Beclin-1 reversed miR-216b-mediated effect on autophagy and apoptosis of NSCLC cells (*P < 0.05,#P < 0.05). Besides, Beclin-1 protein expression was regulated by PVT1 and miR-216b (*P < 0.05, #P < 0.05).

Conclusions

PVT1 may function as a competing endogenous RNA for miR-216b to inhibit cisplatin sensitivity of NSCLC through regulating apoptosis and autophagy via miR-216b/Beclin-1 pathway, providing a novel target for improving chemo-therapy efficacy of NSCLC.
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Metadata
Title
The PVT1/miR-216b/Beclin-1 regulates cisplatin sensitivity of NSCLC cells via modulating autophagy and apoptosis
Authors
Liangfeng Chen
Xiaobing Han
Zhongzhou Hu
Liangxin Chen
Publication date
01-05-2019
Publisher
Springer Berlin Heidelberg
Keywords
NSCLC
NSCLC
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03808-3

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