Guo Kun, Zhang Yun, Liu Lizhi, Meng Hua
Department of Gastroenterology, Caoxian People's Hospital Heze 274400, Shandong Province, China.
Department of General Surgery, Linyi People's Hospital Dezhou 251500, Shandong Province, China.
Am J Transl Res. 2021 Sep 15;13(9):10233-10247. eCollection 2021.
Colon cancer is a common gastrointestinal tumor with complex pathological process. Recently, the relationship between long non-coding RNA (lncRNA) and colon cancer has attracted more and more attention, whereas the underlying molecular mechanism is still poorly understood. Here, we found that the expression of lncRNA small nucleolar RNA host gene 12 (SNHG12) was markedly upregulated in colon cancer samples compared to normal adjacent tissues. Notably, patients with low expression of SNHG12 displayed higher survival rate than those with high expression of SNHG12. Further researches revealed that knockdown of SNHG12 suppressed the malignant phenotype of colon cancer cells. Interestingly, SNHG12 could function as a sponge to specifically bind to microRNA-15a (miR-15a). Moreover, we confirmed that pyruvate dehydrogenase kinase 4 (PDK4) is a direct target gene of miR-15a. Finally, inhibiting miR-15a expression largely abolished the effect of SNHG12 silencing on colon cancer cells. In conclusion, our data uncovered the critical role of SNHG12 in the development and progression of colon cancer through regulating the miR-15a/PDK4 axis, therefore providing a promising target for treating this disease.
结肠癌是一种常见的胃肠道肿瘤,其病理过程复杂。近年来,长链非编码RNA(lncRNA)与结肠癌之间的关系越来越受到关注,但其潜在的分子机制仍知之甚少。在此,我们发现与正常相邻组织相比,lncRNA小核仁RNA宿主基因12(SNHG12)在结肠癌样本中的表达明显上调。值得注意的是,SNHG12低表达的患者比SNHG12高表达的患者生存率更高。进一步研究表明,敲低SNHG12可抑制结肠癌细胞的恶性表型。有趣的是,SNHG12可以作为海绵特异性结合微小RNA-15a(miR-15a)。此外,我们证实丙酮酸脱氢酶激酶4(PDK4)是miR-15a的直接靶基因。最后,抑制miR-15a的表达在很大程度上消除了SNHG12沉默对结肠癌细胞的影响。总之,我们的数据揭示了SNHG12通过调节miR-15a/PDK4轴在结肠癌发生发展中的关键作用,因此为治疗这种疾病提供了一个有前景的靶点。