Regulatory Mechanism of lncRNA CTBP1-AS2 in Nasopharyngeal Carcinoma Cell Proliferation and Apoptosis via the miR-140-5p/BMP2 Axis

Protein Pept Lett. 2022;29(7):621-630. doi: 10.2174/0929866529666220726151339.

Abstract

Objective: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma. LncRNA CTBP1-AS2 (CTBP1-AS2) has effects on tumor cell growth. This study explored the mechanism of CTBP1-AS2 on NPC cells.

Methods: CTBP1-AS2 expressions in immortalized nasopharyngeal epithelial (NP69) and 6 human NPC cells were detected by RT-qPCR and SUNE-1/CNE-1 cells with relative high/low expressions were selected. Cell proliferation and apoptosis were detected by CCK-8, colony formation assays, and flow cytometry. The binding sites between CTBP1-AS2 and miR-140-5p and miR-140-5p and BMP2 were predicted, and the binding relationships were verified by dual-luciferase assay. BMP2 level was detected by Western blot. miR-140-5p was silenced, or BMP2 was overexpressed in SUNE-1 cells with si-CTBP1-AS2 to study the effects of miR-140-5p and BMP2 on CTBP1-AS2 silencing-inhibited malignant behaviors.

Results: CTBP1-AS2 was upregulated in NPC cells. CTBP1-AS2 silencing suppressed NPC cell proliferation and promoted apoptosis. CTBP1-AS2 silencing in SUNE-1 cells raised miR-140-5p expression and repressed BMP2 level. CTBP1-AS2 overexpression in CNE-1 cells suppressed miR- 140-5p expression and elevated BMP2 levels.

Discussion: In mechanism, miR-140-5p overexpression decreased BMP2 levels, reduced NPC cell proliferation, and promoted apoptosis. miR-140-5p knockdown or BMP2 overexpression enhanced NPC cell proliferation and inhibited apoptosis, thus restoring NPC cell malignant behaviors inhibited by silencing CTBP1-AS2.

Conclusion: CTBP1-AS2 decreased miR-140-5p-induced BMP2 inhibition via functioning as a ceRNA of miR-140-5p and promoted BMP2 expression, thereby promoting NPC cell proliferation and suppressing apoptosis.

Keywords: BMP2; LncRNA CTBP1-AS2; Nasopharyngeal carcinoma; apoptosis; ceRNA; immortalized nasopharyngeal epithelial cells; miR-140-5p; proliferation; subcellular localization.

MeSH terms

  • Alcohol Oxidoreductases
  • Apoptosis / genetics
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sincalide / genetics
  • Sincalide / metabolism

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • DNA-Binding Proteins
  • MicroRNAs
  • Mirn140 microRNA, human
  • RNA, Long Noncoding
  • Alcohol Oxidoreductases
  • C-terminal binding protein
  • Sincalide