|
|
|
|
Sunday, May.5, 2024
|
|
|
|
|
|
| miRNA: |
hsa-miR-107 |
| Disease: |
pancreatic cancer |
Relationship type: |
Unspecified |
Detection method for miRNA expression: |
northern blot, qRT-PCR etc |
| Expression pattern of miRNA: |
up-regulated |
Validated targets of miRNA from the reference: |
unknown |
Validated targets of miRNA from TarBase: |
unknown : More... |
| Predicted targets: |
MIRANDA, TARGETSCAN, PICTAR-VERT |
Description: Aberrant expression of microRNAs (miRNAs) has emerged as an important hallmark of cancer. However, the putative mechanisms regulating miRNAs per se are only partially known. It is well established that many tumor suppressor genes in human cancers are silenced by chromatin alterations, including promoter methylation and histone deacetylation. We postulated that miRNAs undergo similar epigenetic inactivation in pancreatic cancer. Two human pancreatic cancer cell lines - MiaPACA-2 and PANC-1 - were treated with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC) or the histone deacetylase inhibitor, trichostatin A, as well as the combination of the two. Expression of miRNAs in control and treated cell lines was assessed using a custom microarray platform. Fourteen miRNAs were upregulated two-fold or greater in each of the cell lines following exposure to both chromatin-modifying agents, including 5 that were in common (miR-107, miR-103, miR-29a, miR-29b, and miR-320) to both MiaPACA-2 and PANC-1. The differential overexpression of miR-107 in the treated cancer cell lines was confirmed by Northern blot assays. Methylation-specific PCR assays for assessment of CpG island methylation status in the 5' promoter region of the miR-107 primary transcript demonstrated complete loss of methylation upon exposure to 5-Aza-dC. Enforced expression of miR-107 in MiaPACA-2 and PANC-1 cells downregulated in vitro growth, and this was associated with repression of the putative miR-107 target, cyclin-dependent kinase 6, thereby providing a functional basis for the epigenetic inactivation of this miRNA in pancreatic cancer. |
Reference:
Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer. | PMID:19407485
Lee KH, Lotterman C, Karikari C, Omura N, Feldmann G, Habbe N, Goggins MG,
Mendell JT, Maitra A
Pancreatology. 2009;9(3):293-301. Epub 2009 Apr 29. |
|
|
|
|
|
|
