Identification of miR-145 targets through an integrated omics analysis.

TitleIdentification of miR-145 targets through an integrated omics analysis.
Publication TypeJournal Article
Year of Publication2015
AuthorsHuang T-C, Renuse S, Pinto S, Kumar P, Yang Y, Chaerkady R, Godsey B, Mendell JT, Halushka MK, Civin CI, Marchionni L, Pandey A
JournalMol Biosyst
Volume11
Issue1
Pagination197-207
Date Published2015 Jan
ISSN1742-2051
KeywordsBinding Sites, Cell Line, Tumor, Computational Biology, Down-Regulation, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Genes, Reporter, Genomics, Humans, MicroRNAs, Proteome, Proteomics, RNA Interference, RNA, Messenger, Transcriptome
Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and protein synthesis. To characterize functions of miRNAs and to assess their potential applications, we carried out an integrated multi-omics analysis to study miR-145, a miRNA that has been shown to suppress tumor growth. We employed gene expression profiling, miRNA profiling and quantitative proteomic analysis of a pancreatic cancer cell line. In our transcriptomic analysis, overexpression of miR-145 was found to suppress the expression of genes that are implicated in development of cancer such as ITGA11 and MAGEA4 in addition to previously described targets such as FSCN1, YES1 and PODXL. Based on miRNA profiling, overexpression of miR-145 also upregulated other miRNAs including miR-124, miR-133b and miR-125a-3p, all of which are implicated in suppression of tumors and are generally co-regulated with miR-145 in other cancers. Using the SILAC system, we identified miR-145-induced downregulation of several oncoproteins/cancer biomarkers including SET, RPA1, MCM2, ABCC1, SPTBN1 and SPTLC1. Luciferase assay validation carried out on a subset of downregulated candidate targets confirmed them to be novel direct targets of miR-145. Overall, this multi-omics approach provided insights into miR-145-mediated tumor suppression and could be used as a general strategy to study the targets of individual miRNAs.

DOI10.1039/c4mb00585f
Alternate JournalMol Biosyst
PubMed ID25354783
PubMed Central IDPMC4352311
Grant ListU54GM103520 / GM / NIGMS NIH HHS / United States
T32 GM007814 / GM / NIGMS NIH HHS / United States
P30 CA006973 / CA / NCI NIH HHS / United States
U54 GM103520 / GM / NIGMS NIH HHS / United States
R01 CA120185 / CA / NCI NIH HHS / United States
HHSN268201000032C / / PHS HHS / United States
U24CA160036 / CA / NCI NIH HHS / United States
U24 CA160036 / CA / NCI NIH HHS / United States
HHSN268201000032C / HL / NHLBI NIH HHS / United States
Related Faculty: 
Luigi Marchionni, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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