Department of Colorectal Surgery, Zhengzhou Anorectal Hospital, Zhengzhou, 450004, China.
Department of Colorectal Surgery, Zhengzhou Anorectal Hospital, Zhengzhou, 450004, China.
Arch Biochem Biophys. 2021 Jul 15;705:108919. doi: 10.1016/j.abb.2021.108919. Epub 2021 May 13.
Baicalin is a traditional Chinese herb purified from the root of Scutellaria baicalensis Georgi. In this study, we further analyzed the molecular mechanism behind the anti-tumor activity of Baicalin in colorectal cancer (CRC). The establishment of circular RNA (circRNA)/microRNA (miRNA)/messenger RNA (mRNA) axis was predicted by bioinformatic databases and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Baicalin dose-dependently reduced the expression of circRNA myosin heavy chain 9 (circMYH9) in CRC cells. Baicalin exposure suppressed the malignant phenotypes of CRC cells, which were largely reversed by the overexpression of circMYH9. CircMYH9 functioned as a molecular sponge for miR-761. CircMYH9 overexpression protected CRC cells from Baicalin-induced injury partly through down-regulating miR-761. MiR-761 interacted with the 3' untranslated region (3' UTR) of hepatoma-derived growth factor (HDGF) mRNA. CircMYH9 up-regulated HDGF expression partly through sponging miR-761 in CRC cells. MiR-761 silencing counteracted the anti-tumor activity of Baicalin partly through up-regulating HDGF in CRC cells. Baicalin suppresses xenograft tumor growth in vivo, and this suppressive effect was partly reversed by the overexpression of circMYH9. In conclusion, Baicalin exhibited an anti-tumor activity in CRC cells partly through down-regulating circMYH9 and HDGF and up-regulating miR-761.
黄芩苷是从黄芩根中提取的一种传统中药。在这项研究中,我们进一步分析了黄芩苷在结直肠癌(CRC)中抗肿瘤活性的分子机制。通过生物信息学数据库预测了环状 RNA(circRNA)/微小 RNA(miRNA)/信使 RNA(mRNA)轴的建立,并通过双荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)实验进行了验证。黄芩苷剂量依赖性地降低 CRC 细胞中环状肌球蛋白重链 9(circMYH9)的表达。黄芩苷暴露抑制了 CRC 细胞的恶性表型,而 circMYH9 的过表达则大大逆转了这种表型。circMYH9 作为 miR-761 的分子海绵发挥作用。circMYH9 的过表达部分通过下调 miR-761 来保护 CRC 细胞免受黄芩苷诱导的损伤。miR-761 与肝癌衍生生长因子(HDGF)mRNA 的 3'非翻译区(3'UTR)相互作用。circMYH9 在 CRC 细胞中部分通过海绵吸附 miR-761 来上调 HDGF 的表达。miR-761 沉默部分通过在 CRC 细胞中上调 HDGF 来抵消黄芩苷的抗肿瘤活性。黄芩苷在体内抑制异种移植肿瘤生长,而过表达 circMYH9 则部分逆转了这种抑制作用。总之,黄芩苷在 CRC 细胞中表现出抗肿瘤活性,部分是通过下调 circMYH9 和 HDGF 以及上调 miR-761 实现的。