Further, the miRNA-target gene network analysis displayed that the deleted in liver cancer (DLC-1) gene, an important negative regulator for cell motility, was potentially targeted by several differentially expressed miRNAs in HBc-introduced cells.
Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1), a Rho GTPase Activating Protein (RhoGAP) previously studied for its function in liver cancer.
Treatment with SAHA or TSA efficiently increased DLC1 expression in all lines, particularly in 22Rv1 cells, and activated the DLC1 promoter through the same Sp1 sites.
Together, our findings indicate that complex formation between the DLC1 START domain and CAV-1 contributes to DLC1 tumor suppression via a RhoGAP-independent mechanism, and suggest that DLC1 inactivation probably contributes to cancer progression.
Consistent with the oncosuppressive function of DLC1 in several cancers, including prostate and liver cancer, transduction of 22Rv1 and 7703K cells with an Ad-DLC1 expression vector resulted in alterations of cell morphology, induction of apoptosis, and inhibition of cell proliferation, migration, and anchorage-independent growth.
Combined, these studies provide information on the mechanism of DLC-1 function and regulation, and further support the role of DLC-1 tumor suppression in NSCLC.
The deleted in liver cancer (DLC-1) gene at chromosome 8p21-22 is altered mainly by genomic deletion or aberrant promoter methylation in a large number of human cancers such as breast, liver, colon and prostate and is known to have an inhibitory effect on breast and liver tumor cell growth.
The DLC-1 gene encoding a regulator of the Rho family of small GTPases is altered in breast, prostate, colon, and liver cancer and has several characteristics of a tumor suppressor gene.
DLC1 (deleted in liver cancer), a gene in this interval, has been proposed as a candidate tumor suppressor gene because of its homology (86% similarity) with rat p122 RhoGAP, which catalyzes the conversion of active GTP-bound rho complex to the inactive GDP-bound form, and thus suppresses Ras-mediated oncogenic transformation.
One of the genes from this region that is expressed by our suppressed hybrids is a candidate tumour suppressor gene, DLC1 (deleted in liver cancer), which has homology to rat RhoGAP.
We investigated the expression and deletion of DLC-1 (frequently deleted in liver cancer gene), first reported in 1998 and having a high homology with rat p122RhoGAP in hepatocellular carcinoma (HCC).