lincRNA-p21 Mediates the Anti-Cancer Effect of Ginkgo Biloba Extract EGb 761 by Stabilizing E-Cadherin Protein in Colon Cancer
Liqiang Chang, Tingting Liu, Zhongqiu Chai, Song Jie, Zhongyun Li, Meilian Liu, Wenhai Dong, Xixing Wang, Bing Zhou
(Department of Anorectal Surgery, Shanxi Provincial Academy of Traditional Chinese Medicine, Taiyuan, Shanxi, China (mainland))
Med Sci Monit 2018; 24:9488-9496
Ginkgo biloba extract EGb 761 is a putative antioxidant and has been used for thousands of years to treat a variety of ailments, including cancer. While it is known that cell behavior can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs in EGb 761-induced anti-cancer effects are largely unknown.
MATERIAL AND METHODS: Colon cancer cell lines HT29 and HCT116 were used in this study. RT-qPCR was used to detect the relative expression of lincRNA-p21 in colon cancer cells. Wound-healing assay and Matrigel Transwell assay were performed to investigate the migration and invasion of colon cancer cells. Immunoprecipitation and Western blot experiments were used to verify ubiquitination and the interaction between lincRNA-p21 and E-cadherin, or E-cadherin and b-transducin repeat containing (BTRC) E3 ubiquitin protein ligase.
RESULTS: Cell function assay verified that treatment with EGb 761 suppressed the migratory and invasive abilities of colon cancer cells in a dose-dependent manner via the suppression of E-cadherin expression level. lincRNA-p21 was upregulated in colon cancer cells after treatment with EGb 761, and knockdown of lincRNA-p21 reversed the EGb 761-induced anti-metastatic effect. Furthermore, lincRNA-p21 was localized in cytoplasm of colon cells and regulated E-cadherin expression at a post-transcriptional level. Specifically, lincRNA-p21 promotes E-cadherin stability by preventing the interaction between BTRC and E-cadherin, which leads to the inhibition of E-cadherin ubiquitination.
CONCLUSIONS: We demonstrated that lincRNA-p21 mediates the anti-cancer effect of Ginkgo biloba extract EGb 761 by stabilizing E-cadherin protein in colon cancer, which may help define the functional role of EGb 761 in cancer treatment.
Keywords: Cadherins, Colonic Neoplasms, RNA, Long Noncoding, ubiquitination