NDLI: Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

Content Provider	PubMed Central
Author	Vishnubalaji, R. Hamam, R. Abdulla, M-h Kassem, M. Al-obeed, O. Aldahmash, A. Alajez, N. M. Mohammed, M. A. V.
Copyright Year	2015
Abstract	Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-β pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R 2=0.56, P=0.0001) and hsa-let-7b-5p (R 2=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC.
Related Links	http://dx.doi.org/10.1038/cddis.2014.556
Starting Page	1614
File Format	PDF
ISSN	20414889
e-ISSN	20414889
Journal	Cell Death & Disease
Issue Number	1
Volume Number	6
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-01-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Cancer Research Immunology Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Genome-Wide Uncovering of STAT3-Mediated miRNA Expression Profiles in Colorectal Cancer Cell Lines

Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

Joint Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease Cortex Reveals Altered miRNA Regulation

Multiple Regression Analysis of mRNA-miRNA Associations in Colorectal Cancer Pathway

Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation.

Genome-Wide Analysis of miRNA-mRNA Interactions in Marrow Stromal Cells

Genome-wide profiling of the microRNA-mRNA regulatory network in skeletal muscle with aging

Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response

Transcription factors expressed in olfactory bulb local progenitor cells revealed by genome-wide transcriptome profiling

Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

Similar Documents

Genome-Wide Uncovering of STAT3-Mediated miRNA Expression Profiles in Colorectal Cancer Cell Lines

Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

Joint Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease Cortex Reveals Altered miRNA Regulation

Multiple Regression Analysis of mRNA-miRNA Associations in Colorectal Cancer Pathway

Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation.

Genome-Wide Analysis of miRNA-mRNA Interactions in Marrow Stromal Cells

Genome-wide profiling of the microRNA-mRNA regulatory network in skeletal muscle with aging

Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response

Transcription factors expressed in olfactory bulb local progenitor cells revealed by genome-wide transcriptome profiling

Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer