Please use this identifier to cite or link to this item: https://doi.org/10.7150/ijbs.60805
Title: MicroRNA-196a promotes renal cancer cell migration and invasion by targeting BRAM1 to regulate SMAD and MAPK signaling pathways
Authors: Cui, Jianzhou 
Yuan, Yi
Shanmugam, Muthu K 
Anbalagan, Durkeshwari
Tan, Tuan Zea 
Sethi, Gautam 
Kumar, Alan Prem 
Lim, Lina HK 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
MicroRNA-196a
renal cancer
Bram1
migration and invasion
SMAD and MAPK pathways
DOWN-REGULATION
NEGATIVE REGULATION
BINDING-PROTEIN
TGF-BETA
MIR-196A
PROLIFERATION
CARCINOMA
METASTASIS
EXPRESSION
CONSEQUENCES
Issue Date: 1-Jan-2021
Publisher: IVYSPRING INT PUBL
Citation: Cui, 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
Abstract: Rationale: 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.
Source Title: INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
URI: https://scholarbank.nus.edu.sg/handle/10635/219259
ISSN: 14492288
DOI: 10.7150/ijbs.60805
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
MicroRNA-196a promotes renal cancer cell migration and invasion by targeting BRAM1 to regulate SMAD and MAPK signaling pathw.pdf3.1 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

4
checked on Sep 23, 2022

Page view(s)

46
checked on Sep 29, 2022

Download(s)

1
checked on Sep 29, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.