Mechanism of PWAR6 regulating cisplatin drug sensitivity in non-small cell lung cancer through miR-577/PHACTR1

Gene. 2024 Jan 30:893:147954. doi: 10.1016/j.gene.2023.147954. Epub 2023 Nov 3.

Abstract

lncRNA Prader Willi/Angelman Region RNA 6 (PWAR6) is considered to play a protective lncRNA in glioma, but, the role of PWAR6 in the occurrence and cisplatin resistance of non-small cell lung cancer (NSCLC) is elusive. In the study, we aimed to assess the role of PWAR6 in the cisplatin resistance of NSCLC. Based on the oebiotech and TargetScanHuman database, we predicted the interaction between PWAR6, miR-577 and PHACTR1. We then used small interfering RNA (siRNA), miRNA mimics and dual-luciferase reporter assay to explore the regulatory role of PWAR6/miR-577PHACTR1. Based on the online database, miR-577 can interact with PWAR6 and PHACTR1. Soon afterwards, we observed that the expression of PWAR6 and PHACTR1 was increased, while miR-577 expression was decreased in A549/DDP cells. And the cell viability was decreased, while cell apoptosis was increased in A549/DDP cells. What's more, PWAR6 knockdown can promote the expression of miR-577 and inhibit the expression of PHACTR1. PWAR6 knockdown elevated cell proliferation and reduced cell apoptosis of A549/DDP cells. Interestingly, we found that miR-577 can interact with PHACTR1 to regulate the proliferation and apoptosis of A549/DDP cells. To conclude, we speculated that PWAR6 knockdown elevated cell proliferation and reduced cell apoptosis of A549/DDP cells via miR-577/PHACTR1, providing the theoretical basis for the clinical treatment of NSCLC patients.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Small Interfering / therapeutic use

Substances

  • Cisplatin
  • Antineoplastic Agents
  • RNA, Long Noncoding
  • MicroRNAs
  • RNA, Small Interfering
  • MIRN577 microRNA, human