|
|
|
Friday, Mar.29, 2024
|
|
|
|
|
|
miRNA: |
hsa-miR-181b-2 |
Disease: |
hepatocellular carcinoma (HCC) |
Relationship type: |
Causal |
Detection method for miRNA expression: |
northern blot, qRT-PCR etc |
Expression pattern of miRNA: |
up-regulated |
Validated targets of miRNA from the reference: |
CDX2, GATA6, NLK |
Validated targets of miRNA from TarBase: |
unknown : More... |
Predicted targets: |
MIRANDA, TARGETSCAN, PICTAR-VERT |
Description: Here, using a global microarray-based miRNA profiling approach followed by validation with quantitative reverse transcription polymerase chain reaction, we have demonstrated that conserved miR-181 family members were up-regulated in EpCAM(+)AFP(+) HCCs and in EpCAM(+) HCC cells isolated from AFP(+) tumors. Moreover, miR-181 family members were highly expressed in embryonic livers and in isolated hepatic stem cells. Importantly, inhibition of miR-181 led to a reduction in EpCAM(+) HCC cell quantity and tumor initiating ability, whereas exogenous miR-181 expression in HCC cells resulted in an enrichment of EpCAM(+) HCC cells. We have found that miR-181 could directly target hepatic transcriptional regulators of differentiation (for example, caudal type homeobox transcription factor 2 [CDX2] and GATA binding protein 6 [GATA6]) and an inhibitor of Wnt/beta-catenin signaling (nemo-like kinase [NLK]). Taken together, our results define a novel regulatory link between miR-181s and human EpCAM(+) liver cancer stem/progenitor cells and imply that molecular targeting of miR-181 may eradicate HCC. |
Reference:
Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. | PMID:19585654
Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C
Hepatology. 2009 Aug;50(2):472-80 |
|
|
|
|
|
|