Circular RNA THBS1 promotes proliferation and apoptosis of non-small cell lung cancer cells by sponging miR-129-5p and regulating SOX4 expression

J BUON. 2020 Jul-Aug;25(4):1721-1727.

Abstract

Purpose: To investigate the influence of circular ribonucleic acid thrombospondin-1 (circTHBS1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells by sponging miR-129-5p and regulating the expression of SRY-box transcription factor 4 (SOX4).

Methods: Carcinoma and para-carcinoma specimens were collected from 40 NSCLC patients, and 25 pairs of specimens were obtained from patients with metastatic and non-metastatic NSCLC. After NSCLC cells were cultured, the proliferation was detected via cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays, and the cell cycle and apoptosis rate were analyzed through flow cytometry. Finally, the action targets of circTHBS1 were determined using dual-luciferase reporter gene assay, and Western blotting assay was applied to measure the changes in protein levels.

Results: The expression of circTHBS1 was markedly higher in NSCLC patients than that in control group, and it was increased in patients with metastatic NSCLC compared with that in patients with non-metastatic NSCLC. Moreover, the proliferative ability of the cells was weakened notably after transfection with small interfering (Si)-CircTHBS1, but it was enhanced remarkably after transfection with CircTHBS1-overexpression vector (OE). There were complementary sites in circTHBS1 for the 3'-UTR of miR-129-5p, and the fluorescence intensity of wild-type circTHBS1 declined evidently after interacting with miR-129-5p. Besides, there was a putative binding site between miR-129-5p and SOX4, and SOX4 expression was decreased obviously after overexpressing miR-129-5p but increased following overexpression of circTHBS1.

Conclusions: CircTHBS1 promotes the proliferation and inhibits the apoptosis of NSCLC cells through targeting miR-129-5p and regulating SOX4 expression.

MeSH terms

  • Apoptosis / physiology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / physiology
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • SOXC Transcription Factors / biosynthesis*
  • SOXC Transcription Factors / metabolism
  • Thrombospondin 1 / metabolism*

Substances

  • MicroRNAs
  • Mirn129 microRNA, human
  • RNA, Circular
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Thrombospondin 1
  • thrombospondin-1, human