RRC ID 45412
Author Beta M, Khetan V, Chatterjee N, Suganeswari G, Rishi P, Biswas J, Krishnakumar S.
Title EpCAM knockdown alters microRNA expression in retinoblastoma--functional implication of EpCAM regulated miRNA in tumor progression.
Journal PLoS One
Abstract The co-ordinated regulation of oncogenes along with miRNAs play crucial role in carcinogenesis. In retinoblastoma (RB), several miRNAs are known to be differentially expressed. Epithelial cell adhesion molecule (EpCAM) gene is involved in many epithelial cancers including, retinoblastoma (RB) tumorigenesis. EpCAM silencing effectively reduces the oncogenic miR-17-92 cluster. In order to investigate whether EpCAM has wider effect as an inducer or silencer of miRNAs, we performed a global microRNA expression profile in EpCAM siRNA knockdown Y79 cells. MicroRNA profiling in EpCAM silenced Y79 cells showed seventy-three significantly up regulated and thirty-six down regulated miRNAs. A subset of these miRNAs was also validated in tumors. Functional studies on Y79 and WERI-Rb-1 cells transfected with antagomirs against two miRNAs of miR-181c and miR-130b showed striking changes in tumor cell properties in RB cells. Treatment with anti-miR-181c and miR-130b showed significant decrease in cell viability and cell invasion. Increase in caspase-3 level was noticed in antagomir transfected cell lines indicating the induction of apoptosis. Possible genes altered by EpCAM influenced microRNAs were predicted by bioinformatic tools. Many of these belong to pathways implicated in cancer. The study shows significant influence of EpCAM on global microRNA expression. EpCAM regulated miR-181c and miR-130b may play significant roles in RB progression. EpCAM based targeted therapies may reduce carcinogenesis through several miRNAs and target genes.
Volume 9(12)
Pages e114800
Published 2014-1-1
DOI 10.1371/journal.pone.0114800
PII PONE-D-14-33372
PMID 25502397
PMC PMC4264963
MeSH Antigens, Neoplasm / genetics* Blotting, Western Cell Adhesion Molecules / genetics* Cell Line, Tumor Collagen Computational Biology Disease Progression Drug Combinations Epithelial Cell Adhesion Molecule Fluorometry Gene Expression Profiling Gene Expression Regulation, Neoplastic / genetics* Gene Knockdown Techniques Humans Laminin MicroRNAs / metabolism* Microarray Analysis Proteoglycans Real-Time Polymerase Chain Reaction Retinoblastoma / genetics Retinoblastoma / metabolism* Reverse Transcriptase Polymerase Chain Reaction
IF 2.74
Times Cited 10
Human and Animal Cells Y79 WERI-Rb-1(RCB2146)