miR-30b-5p inhibits cancer progression and enhances cisplatin sensitivity in lung cancer through targeting LRP8

Apoptosis. 2021 Jun;26(5-6):261-276. doi: 10.1007/s10495-021-01665-1. Epub 2021 Mar 29.

Abstract

Accumulated evidence has demonstrated that miRNAs are closely implicated in lung carcinogenesis. Herein, we explored the expression pattern of miR-30b-5p in lung cancer, and aimed to uncover miR-30b-5p roles in lung cancer progression and drug resistance. miR-30b-5p expression profiles in lung cancer tissues and the matched non-tumor tissues were determined by using qPCR. Cell viability, migration, invasion and in vivo tumorigenesis were determined by using the CCK-8, colony formation, wound healing, transwell chambers experiments and tumor xenograft models. RNA immunoprecipitation (RIP) and dual luciferase reporter experiments were applied to evaluate the relationship between miR-30b-5p and LRP8. The results demonstrated that miR-30b-5p showed a low expression profile in lung cancer tissues and cells, and closely linked to poor prognosis and malignant clinical process. Cell viability, migration, invasiveness and tumorigenesis were significantly weakened following miR-30b-5p overexpression in A549 and NCI-H1299 cells, while cell apoptosis rates were increased. In addition, miR-30b-5p was lowly expressed in A549/DDP (a cisplatin drug resistant cell line) as compared with A549 cells, and miR-30b-5p increased A549/DDP cell sensitivity to DDP. However, these above roles of miR-30b-5p were all significantly impaired following the overexpression of LRP8 which was overexpressed in lung cancer tissues. Collectively, this study demonstrated that miR-30b-5p functions as a tumor suppressor in lung cancer, and re-sensitizes lung cancer cells to DDP by targeting LRP8.

Keywords: Cisplatin; Growth; LRP8; MiR-30b-5p; Migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • LDL-Receptor Related Proteins / genetics*
  • LDL-Receptor Related Proteins / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis

Substances

  • LDL-Receptor Related Proteins
  • MIRN30b microRNA, human
  • MicroRNAs
  • low density lipoprotein receptor-related protein 8
  • Cisplatin