Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Recent studies showed that snRNPs were implicated in human cancer development. The role of SNRPA1, which is a member of U2 snRNPs, in HCC, remains undocumented. Here, we found that SNRPA1 was highly expressed in HCC tissue compared with normal adjacent liver tissues. Up-regulation of SNRPA1 was correlated with the clinical stage of HCC and the overall survival of HCC patients. In vitro and in vivo results showed that knockdown of SNPRA1 inhibited the cell proliferation, colony formation and xenografted tumorigenesis of HCC cells. Apoptosis was induced by SNPRA1 down-regulation. Mechanistically, SNPRA1 was stimulated by mTOR activation. In addition, whole-genome microarray analysis identified that 262 genes were up-regulated and 462 genes were down-regulated by SNPRA1 knockdown in HCC cells. qPCR analysis suggested that the fibroblast growth factor-2 (FGF2), Alpha-fetoprotein (AFP), β-catenin, Ki-67 and cyclin B1 were down-regulated and caspase 3, p53 as well as p21 were up-regulated after SNRPA1 knockdown. Taken together, our findings implicate that SNPRA1 functions as an oncogene in HCC.
Highlights
Hepatocellular carcinoma is fifth most common cancer and the second leading cause of cancer death in worldwide [1,2]
We identify SNRPA1, which is active by mammalian target of rapamycin (mTOR) signaling, as an oncogenic protein and a poor prognostic factor in hepatocellular carcinoma to promote cell proliferation and survival
SNRPA1 knockdown increased the apoptosis of both BEL-7404 and SMMC-7721 cells, suggesting that SNRPA1 knockdown inhibits the viability of hepatocellular carcinoma (HCC) cells partly through inducing apoptosis
Summary
Hepatocellular carcinoma is fifth most common cancer and the second leading cause of cancer death in worldwide [1,2]. The treatment options are limited and the effectiveness is far from satisfactory with poor prognosis for HCC patients. Understanding the pathogenic factors in tumorigenesis may help explore novel and promising targets for HCC. Splicing of pre-mRNA into mRNA in eukaryotes is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein complex composed of small nuclear RNAs (snRNAs) and small nuclear ribonucleoproteins (snRNPs) [3,4]. The spliceosome is correlated with cancer progression as mutation of some spliceosome components are found in various cancers, such as chronic lymphocytic leukemia [6], breast cancer [7], lung adenocarcinoma [8], clear cell carcinoma [9] and uveal melanoma [10]. Mutations are detected mainly in U2 snRNPs and U2-related proteins [11]. SNRPA1 is one of U2 snRNPs, the role of SNRPA1 in HCC is unclear
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