Long non-coding RNA DSCAM-AS1 accelerates the progression of hepatocellular carcinoma via sponging miR-338-3p

摘要

Aberrant expression of long non-coding RNA DSCAM-AS1 (Down Syndrome Cell Adhesion Molecule antisense) has been observed in several cancers. However, the expression status, biological function and underling mechanism of DSCAM-AS1 in hepatocellular carcinoma (HCC) remain unclear. The expression of DSCAM-AS1 was detected in HCC tissues and serum from both HCC patients and healthy controls. MTS, wound healing and transwell invasion assays were used to examine the effects of DSCAM-AS1 on cell proliferation, migration, and invasion in HCC cells, respectively. MicroRNAs (miRNAs) targeted DSCAM-AS1 was predicated by Starbase2.0 and identified using luciferase reporter and RNA immunoprecipitation assays. The xenograft mice were established to examine the effect DSCAM-AS1 on tumor growth in vivo. We found that DSCAM-AS1 was up-regulated in HCC tissues relative to adjacent non-tumor tissues. Serum levels of DSCAM-AS1 were higher in HCC patients than that in healthy controls. Increased DSCAM-AS1 was associated with poor prognosis. Knockdown of DSCAM-AS1 significantly inhibited HCC cell proliferation, migration and invasion. Moreover, miR-338-3p was confirmed as a direct target of DSCAM-AS1 in HCC cells. The miR-338-3p inhibitor could partially reverse the inhibitory effect of DSCAM-AS1 depletion in HCC cells. DSCAM-AS1 positively regulated CyclinD1 and smoothened (SMO) expression (two targets of miR-338-3p) in HCC cells. Moreover, tumor growth was tremendously retarded in nude mice received injection of SMCC-7721 cells transfected with sh-DSCAM-AS1. Taken together, the present work suggested that DSCAM-AS1 functioned as an oncogenic lncRNA that promoted HCC progression by sponging miR-338-3p.