Abstract
BackgroundHepatocellular carcinoma (HCC) is a common cancer leading to high morbidity and mortality in worldwide. Previous studies revealed that SEC61 translocon alpha 1 subunit1 (SEC61A) can act as an oncogene in colon adenocarcinoma. However, the functions and molecular mechanism associated with HCC progression remain to be explored. This study aimed at exploring the role of SEC61A1 in HCC progression.MethodsEdU assay and colony formation assay were applied to assess cell proliferation. The migratory ability of transfected HCC cells was evaluated by transwell migration assay. Sphere formation assay was used to detect the stemneess of HCC cells. Bioinformatics analysis tools and mechanism experiments were used to predict and analyze the potential molecular mechanism associated with the upregulation of SEC61A1 in HCC cells.ResultsUp-regulated SEC61A1 facilitated cell proliferation, migration and stemness in HCC cells. MiR-491-5p negatively regulated SEC61A1 and inhibited HCC cell proliferation and migration by targeting SEC61A1. VPS9D1 antisense RNA 1 (VPS9D1-AS1) could up-regulate SEC61A1 through sponging miR-491-5p. Early growth response 1 (EGR1) was identified as the upstream transcriptional activator for both SEC61A1 and VPS9D1-AS1.ConclusionsOur study unveiled a novel molecular pathway facilitating HCC cell proliferation, migration and stemness, which may shed new insight into HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) is a common cancer leading to high morbidity and mortality in worldwide
The results revealed that SEC61 translocon alpha subunit (SEC61A1) was significantly up-regulated in HCC cell lines (Fig. 1a)
VPS9D1‐AS1 serves as a sponge of miR‐491‐5p to up‐regulate SEC61A1 Since Long non-coding RNA (lncRNA) are reported as miRNAs’ sponges to upregulate mRNAs, we explored whether the inhibitory effect of miR-491-5p on SEC61A1 could be attenuated by a certain lncRNA
Summary
Hepatocellular carcinoma (HCC) is a common cancer leading to high morbidity and mortality in worldwide. Previous studies revealed that SEC61 translocon alpha 1 subunit (SEC61A) can act as an oncogene in colon adenocarcinoma. The functions and molecular mechanism associated with HCC progression remain to be explored. This study aimed at exploring the role of SEC61A1 in HCC progression. Despite great advancements for HCC therapies in recent years, the 5-year survival rate of HCC patients remains disappointing due to SEC61 translocon alpha 1 subunit (SEC61A1) was previously reported to contribute to progression of colon adenocarcinoma via the MNX1-AS1-miR-218-5pSEC61A1 network [5]. The present study was designed to explore the function as well as the underlying mechanism of SEC61A1 in HCC. LncRNA ID2-AS1 suppresses HCC metastasis through activation of HDAC8/ID2 pathway
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