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

Abstract

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. 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. 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. 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. 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.