miR‑454‑3p inhibits non‑small cell lung cancer cell proliferation and metastasis by targeting TGFB2

Oncol Rep. 2021 May;45(5):67. doi: 10.3892/or.2021.8018. Epub 2021 Mar 24.

Abstract

Accumulating studies have suggested that microRNAs (miRs) play a significant role in lung cancer development and progression, especially in non‑small cell lung cancer (NSCLC). The present study aimed to investigate the associations between miR‑454‑3p and NSCLC progression. qPCR assay was applied to examine the expression of miR‑454‑3p and transforming growth factor‑β2 (TGFB2) in tissues and cell lines. CCK‑8 and EdU assays were used to detect cell proliferation. Wound‑healing and Transwell assays were conducted to assess cell migration and invasion. Western blotting assay was performed to explore the protein levels of epithelial‑mesenchymal transition (EMT) markers. The interaction between miR‑454‑3p and TGFB2 was investigated with a luciferase reporter assay. miR‑454‑3p was downregulated in NSCLC tissues and NSCLC cell lines. miR‑454‑3p overexpression led to the suppression of proliferation, migration, and invasion in A549 and NCI‑H1650 cells. In addition, the overexpression of miR‑454‑3p in A549 and NCI‑H1650 cells significantly inhibited EMT. TGFB2 was revealed to be a direct target of miR‑454‑3p by using TargetScan database and luciferase reporter assay. TGFB2 was observed to be upregulated in NSCLC tissues and cell lines. Further mechanistic studies revealed that the inhibitory effects of miR‑454‑3p on NSCLC were reversed upon overexpression of TGFB2. These findings provided strong evidence that miR‑454‑3p suppressed NSCLC cell proliferation and metastasis by targeting TGFB2. The study suggests that targeting miR‑454‑3p could be a promising strategy for treating NSCLC.

Keywords: non‑small cell lung cancer; microRNA‑454‑3p; transforming growth factor‑β2; proliferation; epithelial‑mesenchymal transition; metastasis.

Publication types

  • Observational Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • A549 Cells
  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Pneumonectomy
  • Transforming Growth Factor beta2 / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN454 microRNA, human
  • MicroRNAs
  • TGFB2 protein, human
  • Transforming Growth Factor beta2