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

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.

Long noncoding RNA TUG1 regulates the progression of colorectal cancer through miR-542-3p/TRIB2 axis and Wnt/ß-catenin pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the third normal malignancy worldwide. Taurine-upregulated gene 1 (TUG1), a member of long noncoding RNAs (lncRNAs), has been reported to be involved in various cancers. However, the mechanism underlying TUG1 in the progression of CRC remains unclear. METHODS: The expression of TUG1, microRNA-542-3p (miR-542-3p), and tribbles homolog 2 (TRIB2) in CRC tissues and cells (LoVo and HCT116) were detected by quantitative real-time PCR (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), transwell and flow cytometry assays were employed to evaluate the effects of TUG1 in CRC cells. The interaction between miR-542-3p and TUG1 or TRIB2 were verified by dual-luciferase reporter assay. A xenograft tumor model in nude mice was established to investigate the biological role of TUG1 in CRC in vivo. RESULTS: TUG1 was increased in CRC tissues and cells (LoVo and HCT116) in contrast with adjacent normal tissues and normal intestinal mucous cells (CCC-HIE-2). Downregulation of TUG1 or TRIB2 suppressed the proliferation, migration, invasion, and induced apoptosis in CRC cells. And knockdown of TUG1 repressed tumor growth in vivo. Besides, overexpression of TRIB2 reversed the effects of TUG1 depletion on the progression of CRC. Meanwhile, TUG1 interacted with miR-542-3p and TRIB2 was a target of miR-542-3p. Furthermore, miR-542-3p knockdown or TRIB2 overexpression partly reversed the suppression effect of TUG1 depletion on the Wnt/ß-catenin pathway. CONCLUSIONS: TUG1 served as a tumor promoter, impeded the progression of CRC by miR-542-3p/TRIB2 axis to inactivate of Wnt/ß-catenin pathway, which providing a novel target for CRC treatment.