CTBP1-AS2 promoted non-small cell lung cancer progression via sponging the miR-623/MMP3 axis

Environ Sci Pollut Res Int. 2022 May;29(25):38385-38394. doi: 10.1007/s11356-021-15921-z. Epub 2022 Jan 25.

Abstract

Mounting evidence indicates that lncRNAs (long noncoding RNAs) are involved in the initiation and development of tumors, including non-small cell lung cancer (NSCLC). However, the involvement of C-terminal binding protein-antisense RNA 2 (CTBP1-AS2) in NSCLC remains to be studied. RT-qPCR was carried out to detect CTBP1-AS2 and miR-623 expression in NSCLC cells and tissues. CCK-8 and flow cytometry were performed to measure cell proliferation and cell cycle progression. Luciferase reporter analysis was performed to study the potential target of CTBP1-AS2. We found that CTBP1-AS2 expression was upregulated in NSCLC cells (SPC-A1, A549, H23, and H1299) compared to 16HBE cells. We demonstrated that the CTBP1-AS2 level was higher in NSCLC specimens than in paired non-tumor specimens. Elevated expression of CTBP1-AS2 increased cell growth and induced cell cycle progression and epithelial-mesenchymal transition (EMT). We also found that ectopic expression of CTBP1-AS2 inhibited miR-623 expression. MMP3 was a direct target of miR-623, and luciferase reporter assays suggested that miR-623 overexpression suppressed the luciferase expression driven by the MMP3 wild-type reporter but not the mutant reporter. Overexpression of miR-623 suppressed MMP3 expression in A549 cells, and overexpression of CTBP1-AS2 increased MMP3 expression in A549 cells. Moreover, the miR-623 level was lower in NSCLC specimens than in paired non-tumor specimens, and CTBP1-AS2 expression was negatively correlated with miR-623 expression in NSCLC samples. Furthermore, overexpression of CTBP1-AS2 enhanced cell growth, cell cycle progression, and EMT progression by modulating MMP3 expression.

Keywords: CTBP1-AS2; MMP3; NSCLC; miR-623.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Matrix Metalloproteinase 3* / genetics
  • Matrix Metalloproteinase 3* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • Signal Transduction

Substances

  • MIRN623 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • MMP3 protein, human
  • Matrix Metalloproteinase 3