The Role of the LINC01234/miR-433-3p/GRB2 ceRNA Network in NSCLC Cell Malignant Proliferation

Comb Chem High Throughput Screen. 2023;26(10):1836-1847. doi: 10.2174/1386207325666220624093957.

Abstract

Background: Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Dysregulation of lncRNAs leads to NSCLC progression.

Objective: This study aims to explore the regulatory mechanism of lncRNA LINC01234 in NSCLC.

Materials and methods: LINC01234 expression in NSCLC cells was determined. Cell proliferation was detected using CCK-8, colony formation, and EDU assays after transfection of siRNA LINC01234 into H1299 cells and transfection of pcDNA3.1-LINC01234 into H1975 cells. Subcellular localization of LINC01234 was predicted and the binding relations between LINC01234 and miR-433-3p as well as miR-433-3p and GRB2 were verified. The expression levels of miR-433-3p and GRB2 in NSCLC cells were determined. Joint experiments of miR-433-3p inhibitor + si- LINC01234-1 or oe-GRB2 + si-LINC01234-1 were conducted to verify the role of miR-433-3p and GRB2 in NSCLC cell malignant proliferation.

Results: LINC01234 was abundantly expressed in NSCLC cells. LINC01234 silencing reduced NSCLC cell proliferation while LINC01234 overexpression enhanced cell proliferation. LINC01234 competitively bound to miR-433-3p and miR-433-3p directly targeted GRB2. miR- 433-3p knockdown or GRB2 overexpression counteracted the repressive effect of LINC01234 silencing on NSCLC cell malignant proliferation.

Conclusion: LINC01234 competitively bound to miR-433-3p and promoted GRB2 transcription to augment NSCLC cell malignant proliferation.

Keywords: EDU; GRB2; LINC01234; Non-small cell lung cancer; colony formation; competing endogenous RNA; malignant proliferation; microRNA-433-3p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • GRB2 Adaptor Protein / genetics
  • GRB2 Adaptor Protein / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • GRB2 protein, human
  • GRB2 Adaptor Protein
  • MIRN433 microRNA, human