PMID- 35293283 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220716 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 13 IP - 4 DP - 2022 Apr TI - Magnesium isoglycyrrhizinate suppresses bladder cancer progression by modulating the miR-26b/Nox4 axis. PG - 7986-7999 LID - 10.1080/21655979.2022.2031677 [doi] AB - Magnesium isoglycyrrhizinate (MI), a magnesium salt of 18alpha-GA stereoisomer, has been reported to exert efficient hepatoprotective activity. However, its effect on bladder cancer remains unclear. The study explored the effects of MI on the growth, colony formation, apoptosis, invasion, and migration of bladder cancer cells (HTB9 and BIU87 cells). Typical apoptotic changes of bladder cancer cells such as nuclear concentration and fragmentation were observed using Hoechst staining. The effects of MI on the expression levels of microRNA-26b (miR-26b), NADPH oxidase 4 (Nox4), nuclear transcription factor-kappaB (NF-kappaB), and hHypoxia inducible factor-1alpha (HIF-1alpha) were detected using qRT-PCR and Western blot. The potential targets of miR-26b were predicted using Targetscan, and their interactions were determined by luciferase reporter assay. A xenograft mouse model was established to evaluate the anti-tumor effects of MI in vivo. MI significantly suppressed the proliferation, colony formation, invasion, and migration and induced apoptosis of human bladder cancer cells, and MI significantly increased miR-26b expression. Nox 4 was identified to be a direct target of miR-26b. MiR-26b mimics significantly decreased the relative luciferase activity of wild type (WT) Nox 4 but not mutant type (MUT) Nox4. Meanwhile, MI markedly downregulated the expression levels of Nox4, NF-kappaB, and HIF-1alpha both in vitro and in vivo. Moreover, MI inhibited xenograft tumor growth in vivo and decreased the expression of Nox4, NF-kappaB, and HIF-1alpha. Overall, MI showed a potent anti-tumor effect against bladder cancer partially via modulating the miR-26b/Nox4 axis. FAU - Yuan, Zhihao AU - Yuan Z AD - Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China. FAU - Guo, Guancheng AU - Guo G AD - Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China. FAU - Sun, Guifang AU - Sun G AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China. FAU - Li, Qi AU - Li Q AD - Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China. FAU - Wang, Lihui AU - Wang L AD - Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China. FAU - Qiao, Baoping AU - Qiao B AUID- ORCID: 0000-0003-0334-4629 AD - Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China. LA - eng PT - Journal Article PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate) RN - 0 (MIRN26A microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NF-kappa B) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - EC 1.6.3.- (NADPH Oxidase 4) RN - EC 1.6.3.- (NOX4 protein, human) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Humans MH - Mice MH - *MicroRNAs/genetics MH - *NADPH Oxidase 4/genetics MH - NF-kappa B/genetics/metabolism MH - *Saponins/pharmacology MH - *Triterpenes/pharmacology MH - *Urinary Bladder Neoplasms/drug therapy/genetics PMC - PMC9161837 OTO - NOTNLM OT - Magnesium isoglycyrrhizinate OT - Nox4/ NF-kappaB/HIF-1alpha OT - apoptosis OT - bladder cancer OT - miR-26b COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/03/17 06:00 MHDA- 2022/04/27 06:00 PMCR- 2022/03/16 CRDT- 2022/03/16 08:43 PHST- 2022/03/16 08:43 [entrez] PHST- 2022/03/17 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/03/16 00:00 [pmc-release] AID - 2031677 [pii] AID - 10.1080/21655979.2022.2031677 [doi] PST - ppublish SO - Bioengineered. 2022 Apr;13(4):7986-7999. doi: 10.1080/21655979.2022.2031677.