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

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.

• Authors: Liangfeng Chen, Xiaobing Han, Zhongzhou Hu, Liangxin Chen
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 83 Issue 5 Pg. 921-931 (05 2019) ISSN: 1432-0843 [Electronic] Germany
• PMID: 30859368 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Beclin-1
• MIRN216 microRNA, human
• MicroRNAs
• PVT1 long-non-coding RNA, human
• RNA, Long Noncoding
• Cisplatin

Topics

• A549 Cells
• Aged
• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Beclin-1 (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Survival (drug effects)
• Cisplatin (administration & dosage, pharmacology)
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Lung Neoplasms (drug therapy)
• Male
• MicroRNAs (genetics)
• Middle Aged
• Prognosis
• RNA, Long Noncoding (genetics)