miR-330-5p靶向PTBP1调控结肠癌凋亡的机制

Mechanism of miR-330-5p targeting PTBP1 to regulate colon cancer apoptosis

[目的]探讨miR-330-5p/PTBP1/CTTN轴调控结肠癌细胞凋亡的潜在机制。[方法]纳入接受根治性结肠切除术的结肠癌患者113例,分析miR-330-5p在结肠癌组织和癌旁组织中的表达水平以及其对总生存率的影响。[结果]miR-330-5p在结肠癌组织中的表达水平较低(0.48±0.22 vs 0.16±0.09,P<0.05)。miR-330-5p高表达的结肠癌患者具有更高的总生存率。过表达miR-330-5p及敲低PTBP1,HCT116细胞的凋亡水平上升(13.02±2.11 vs 68.41±11.08, 12.84±2.16 vs 59.12±10.53,P<0.05)。过表达miR-330-5p后,HCT116细胞中PTBP1的mRNA水平和蛋白水平均下降(0.39±0.04 vs 0.05±0.01,P<0.05)。敲低CTTN后,HCTT6细胞的凋亡水平显著上升(11.70±2.05 vs 55.73±10.19,P<0.05)。过表达miR-330-5p或PTBP1敲低后,CTTN isoform a的表达水平下降。[结论]miR-330-5p能够靶向降解PTBP1 mRNA,减少PTBP1的表达水平,促进结肠癌细胞凋亡。miR-330-5p/PTBP1轴能够调控CTTN外显子的选择性剪接,抑制CTTN isoform a的表达水平并促进结肠癌细胞凋亡。

[Objective]To explore the potential mechanism of miR-330-5p/PTBP1/CTTN axis regulating colon cancer cell apoptosis.[Method]113 colon cancer patients who received radical colectomy were enrolled in this study to analyze the expression level of miR-330-5p in colon cancer tissues and adjacent tissues and its impact on the overall survival rate.[Result]The expression level of miR-330-5p in colon cancer was lower(0.48±0.22 us 0.16±0.09,P<0.05).Colon cancer patients with high expression of miR-330-5p have a higher overall survival rate.Overexpression of miR-330-5p and knockdown of PTBP1 increased the apoptosis level of HCT116 cells(13.02±2.11 us 68.41±11.08,12.84±2.16 us 59.12±10.53,P<0.05).After overexpression of miR-330-5p,the mRNA and protein levels of PTBP1 in HCT116 cells decreased(0.39±0.04 us 0.05±0.01,P<0.05).After knockdown of CTTN,the apoptosis level of HCTT6 cells increased significantly(11.70±2.05 us 55.73±10.19,P<0.05).After overexpression of miR-330-5p or knockdown of PTBP1,the expression level of CTTN isoform a decreased.[Conclusion]MiR-330-5p can target the degradation of PTBPI mRNA,reduce the expression level of PTBPI,and promote the apoptosis of colon cancer cells.The miR-330-5p/PTBPI axis can regulate the alternative splicing of CTTN exons,inhibit the expression level of CTTN isoform a and promote the apoptosis of colon cancer cells.