Please use this identifier to cite or link to this item: https://doi.org/10.7150/ijbs.60805
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dc.titleMicroRNA-196a promotes renal cancer cell migration and invasion by targeting BRAM1 to regulate SMAD and MAPK signaling pathways
dc.contributor.authorCui, Jianzhou
dc.contributor.authorYuan, Yi
dc.contributor.authorShanmugam, Muthu K
dc.contributor.authorAnbalagan, Durkeshwari
dc.contributor.authorTan, Tuan Zea
dc.contributor.authorSethi, Gautam
dc.contributor.authorKumar, Alan Prem
dc.contributor.authorLim, Lina HK
dc.date.accessioned2022-04-19T01:15:45Z
dc.date.available2022-04-19T01:15:45Z
dc.date.issued2021-01-01
dc.identifier.citationCui, Jianzhou, Yuan, Yi, Shanmugam, Muthu K, Anbalagan, Durkeshwari, Tan, Tuan Zea, Sethi, Gautam, Kumar, Alan Prem, Lim, Lina HK (2021-01-01). MicroRNA-196a promotes renal cancer cell migration and invasion by targeting BRAM1 to regulate SMAD and MAPK signaling pathways. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 17 (15) : 4254-4270. ScholarBank@NUS Repository. https://doi.org/10.7150/ijbs.60805
dc.identifier.issn14492288
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/219259
dc.description.abstractRationale: MicroRNAs (miRNAs) are endogenous ~22nt RNAs that play critical regulatory roles in various biological and pathological processes, including various cancers. Their function in renal cancer has not been fully elucidated. It has been reported that miR-196a can act as oncogenes or as tumor suppressors depending on their target genes. However, the molecular target for miR-196a and the underlying mechanism in miR-196a promoted cell migration and invasion in renal cancer is still not clear. Methods: The expression, survival and correlation between miR-196a and BRAM1 were investigated using TCGA analysis and validated by RT-PCR and western blot. To visualize the effect of Bram1 on tumor metastasis in vivo, NOD-SCID gamma (NSG) mice were intravenously injected with RCC4 cells (106 cells/mouse) or RCC4 overexpressing Bram1. In addition, cell proliferation assays, migration and invasion assays were performed to examine the role of miR-196a in renal cells in vitro. Furthermore, immunoprecipitation was done to explore the binding targets of Bram1. Results: TCGA gene expression data from renal clear cell carcinoma patients showed a lower level of Bram1 expression in patients’ specimens compared to adjacent normal tissues. Moreover, Kaplan-Meier survival data clearly show that high expression of Bram1correlates to poor prognosis in renal carcinoma patients. Our mouse metastasis model confirmed that Bram1 overexpression resulted in an inhibition in tumor metastasis. Target-prediction analysis and dual-luciferase reporter assay demonstrated that Bram1 is a direct target of miR-196a in renal cells. Further, our in vitro functional assays revealed that miR-196a promotes renal cell proliferation, migration, and invasion. Rescue of Bram1 expression reversed miR-196a-induced cell migration. MiR-196a promotes renal cancer cell migration by directly targeting Bram1 and inhibits Smad1/5/8 phosphorylation and MAPK pathways through BMPR1A and EGFR. Conclusions: Our findings thus provide a new mechanism on the oncogenic role of miR-196a and the tumor-suppressive role of Bram1 in renal cancer cells. Dysregulated miR-196a and Bram1 represent potential prognostic biomarkers and may have therapeutic applications in renal cancer.
dc.language.isoen
dc.publisherIVYSPRING INT PUBL
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectBiology
dc.subjectLife Sciences & Biomedicine - Other Topics
dc.subjectMicroRNA-196a
dc.subjectrenal cancer
dc.subjectBram1
dc.subjectmigration and invasion
dc.subjectSMAD and MAPK pathways
dc.subjectDOWN-REGULATION
dc.subjectNEGATIVE REGULATION
dc.subjectBINDING-PROTEIN
dc.subjectTGF-BETA
dc.subjectMIR-196A
dc.subjectPROLIFERATION
dc.subjectCARCINOMA
dc.subjectMETASTASIS
dc.subjectEXPRESSION
dc.subjectCONSEQUENCES
dc.typeArticle
dc.date.updated2022-04-18T08:41:34Z
dc.contributor.departmentDEAN'S OFFICE (MEDICINE)
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.7150/ijbs.60805
dc.description.sourcetitleINTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
dc.description.volume17
dc.description.issue15
dc.description.page4254-4270
dc.published.statePublished
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