hsa-miR-1

lung cancer

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

C/EBPa, MET, FoxP1, HDAC4,

Validated targets of miRNA from TarBase:

GJA1,Hand2,HDAC4,TMSB4X : More...

Description:

we report that microRNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down regulated in human primary lung cancer tissues and cell lines. In situ hybridization demonstrated localization of miR-1 in bronchial epithelial cells. The tumor suppressor C/EBPa, frequently suppressed in lung cancer reactivated miR-1 expression in the lung cancer cells. Repressed miR-1 was also activated in lung cancer cells upon treatment with a histone deacetylase inhibitor. Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties such as growth, replication potential, motility/migration, clonogenic survival and tumor formation in nude mice. Exogenous miR-1 significantly reduced expression of oncogenic targets such as MET, a receptor tyrosine kinase, and Pim-1, a ser/thr kinase, frequently upregulated in lung cancer. Similarly, the level of two additional targets, FoxP1, a transcription factor with oncogeneic property, and HDAC4 that represses differentiation-promoting genes, was reduced in miR-1 expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth with concomitant elevation of these targets. Further, ectopic miR-1 induced apoptosis in A549 cells in response to the potent anticancer drug doxorubicin (DOXR). Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1 and depletion of antiapoptotic Mcl-1 contributed to the sensitivity of miR-1 expressing cells to DOXR. Thus, miR-1 has potential therapeutic application against lung cancers.

Reference:

Downregulation of microRNA-1 (miR-1) in lung cancer: Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin induced apoptosis bymiR-1. | PMID:18818206
Nasser MW, Datta J, Nuovo G, Kutay H, Motiwala T, Majumder S, Wang B, Suster S, Jacob ST, Ghoshal K.
J Biol Chem. 2008 Sep 25. [Epub ahead of print]