Systematic analysis of berberine-induced signaling pathway between miRNA clusters and mRNAs and identification of mir-99a∼125b cluster function by seed-targeting inhibitors in multiple myeloma cells
- 2 January 2015
- journal article
- research article
- Published by Taylor & Francis Ltd in RNA Biology
- Vol. 12 (1), 82-91
- https://doi.org/10.1080/15476286.2015.1017219
Abstract
Background: Berberine (BBR) is a natural alkaloid derived from a traditional Chinese herbal medicine. However, the exact mechanisms underlying the different effects of berberine on MM cells have not been fully elucidated. Methods: A systematic analysis assay integrated common signaling pathways modulated by the 3 miRNA clusters and mRNAs in MM cells after BBR treatment. The role of the mir-99a similar to 125b cluster, an important oncomir in MM, was identified by comparing the effects of t-anti-mirs with complete complementary antisense locked nucleic acids (LNAs) against mature mir-125b (anti-mir-125b). Results: Three miRNAs clusters (miR-99a similar to 125b, miR-17 similar to 92 and miR-106 similar to 25) were significantly down-regulated in BBR-treated MM cells and are involved in multiple cancer-related signaling pathways. Furthermore, the top 5 differentially regulated genes, RAC1, NF kappa B1, MYC, JUN and CCND1 might play key roles in the progression of MM. Systematic integration revealed that 3 common signaling pathways (TP53, Erb and MAPK) link the 3 miRNA clusters and the 5 key mRNAs. Meanwhile, both BBR and seed-targeting t-anti-mir-99a similar to 125b cluster LNAs significantly induced apoptosis, G2-phase cell cycle arrest and colony inhibition. Conclusions: our results suggest that BBR suppresses multiple myeloma cells, partly by down-regulating the 3 miRNA clusters and many mRNAs, possibly through TP53, Erb and MAPK signaling pathways. The mir-99a similar to 125b cluster might be a novel target for MM treatment. These findings provide new mechanistic insight into the anticancer effects of certain traditional Chinese herbal medicine compounds.Keywords
This publication has 42 references indexed in Scilit:
- MicroRNA-21-3p, a Berberine-Induced miRNA, Directly Down-Regulates Human Methionine Adenosyltransferases 2A and 2B and Inhibits Hepatoma Cell GrowthPLOS ONE, 2013
- Targeting p53 via JNK Pathway: A Novel Role of RITA for Apoptotic Signaling in Multiple MyelomaPLOS ONE, 2012
- Silencing of microRNA families by seed-targeting tiny LNAsNature Genetics, 2011
- Drug Inhibition Profile Prediction for NFκB Pathway in Multiple MyelomaPLOS ONE, 2011
- Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma DevelopmentCancer Cell, 2010
- Negative regulation of the tumor suppressor p53 gene by microRNAsOncogene, 2010
- RhoA and Rac1 GTPases play major and differential roles in stromal cell–derived factor-1–induced cell adhesion and chemotaxis in multiple myelomaBlood, 2009
- Genetic events in the pathogenesis of multiple myelomaBest Practice & Research Clinical Haematology, 2007
- OncomiRs: the discovery and progress of microRNAs in cancersMolecular Cancer, 2007
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006