| 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
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
Y79
WERI-Rb-1(RCB2146) |
