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采用邱氏 5 步法研究黄芩苷抑制结直肠癌细胞恶性表型和诱导细胞凋亡的作用机制。

Use Chou's 5-steps rule to study how Baicalin suppresses the malignant phenotypes and induces the apoptosis of colorectal cancer cells.

机构信息

Department of Colorectal Surgery, Zhengzhou Anorectal Hospital, Zhengzhou, 450004, China.

Department of Colorectal Surgery, Zhengzhou Anorectal Hospital, Zhengzhou, 450004, China.

出版信息

Arch Biochem Biophys. 2021 Jul 15;705:108919. doi: 10.1016/j.abb.2021.108919. Epub 2021 May 13.

Abstract

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.

摘要

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。

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