长链非编码 RNA CTBP1-AS2 通过 miR-140-5p/BMP2 轴调控鼻咽癌细胞增殖和凋亡的机制研究。

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

机构信息

Department of Otorhinolaryngology Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

Department of Otorhinolaryngology Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, 530021, Guangxi Zhuang Autonomous Region, China.

出版信息

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

DOI:10.2174/0929866529666220726151339

PMID:35894463

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.

摘要

目的

鼻咽癌（NPC）是一种鳞状细胞癌。长链非编码 RNA CTBP1-AS2（CTBP1-AS2）对肿瘤细胞生长有影响。本研究探讨了 CTBP1-AS2 对 NPC 细胞的作用机制。

方法

采用 RT-qPCR 检测永生化鼻咽上皮（NP69）细胞和 6 种人 NPC 细胞中 CTBP1-AS2 的表达情况，选择相对高/低表达的 SUNE-1/CNE-1 细胞。采用 CCK-8 法、集落形成实验和流式细胞术检测细胞增殖和凋亡。预测 CTBP1-AS2 与 miR-140-5p 及 miR-140-5p 与 BMP2 的结合位点，并通过双荧光素酶报告实验验证结合关系。采用 Western blot 检测 BMP2 水平。用 si-CTBP1-AS2 沉默 SUNE-1 细胞中的 miR-140-5p 或过表达 BMP2，研究 miR-140-5p 和 BMP2 对 CTBP1-AS2 沉默抑制恶性行为的影响。

结果

CTBP1-AS2 在 NPC 细胞中上调。CTBP1-AS2 沉默抑制 NPC 细胞增殖，促进细胞凋亡。SUNE-1 细胞中 CTBP1-AS2 沉默上调 miR-140-5p 表达，下调 BMP2 水平。CNE-1 细胞中 CTBP1-AS2 过表达下调 miR-140-5p 表达，上调 BMP2 水平。