Long non‐coding RNA VPS9D1-AS1 facilitates cell proliferation, migration and stemness in hepatocellular carcinoma

Abstract

Background Hepatocellular 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. Methods EdU 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. Results Up-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. Conclusions Our study unveiled a novel molecular pathway facilitating HCC cell proliferation, migration and stemness, which may shed new insight into HCC treatment.

A Risk Model Based on Sorafenib-Response Target Genes Predicts the Prognosis of Patients with HCC

“…Preliminary evidence suggests that the anticancer effects of sorafenib in HCC patients are related to these mechanisms. e results of previous studies have confirmed that SLC41A3, SEC61A1, LRP4, PPM1G, and HSP90AA1 play important roles in cancer progression [28][29][30][31][32][33][34][35][36][37][38][39]. SLC41A3 is a member of solute carrier family 41 and is involved in many cellular processes.…”

“…miR-491-5p inhibits HCC cell proliferation and migration by regulating SEC61A1 expression. VPS9D1-AS1 can upregulate SEC61A1 expression by sponging miR-491-5p, which in turn is involved in HCC growth and metastasis [ 30 ]. PPM1G is overexpressed in HCC tissues and associated with HCC metastasis, the pathological grade, microvascular invasion, and hepatitis B virus (HBV) infection.…”

Characterization of Cell Cycle-Related Competing Endogenous RNAs Using Robust Rank Aggregation as Prognostic Biomarker in Lung Adenocarcinoma

“…One of its regulators, miR-30a-5p, also has been widely of concern as an important miRNA, especially for its role via crosstalk with other RNAs in some pathways in different cancers (67)(68)(69). The overexpression of another ncRNA, lncRNA VPS9D1-AS1, a potential prognostic marker, can be used to predict poor prognosis in NSCLC (70), and its role in cancer has been validated (71,72). All of these RNAs have been validated with roles in tumorigenesis, and this axis may be a proper marker to predict cancer progression.…”

Evaluating the Effect of Lenvatinib on Sorafenib-Resistant Hepatocellular Carcinoma Cells

“…Decreased miR-491-5p and highly pyruvate kinase M2 (PKM2) expression were associated with unfavorable clinical features and the poor prognosis of HCC patients [ 46 ]. In addition, overexpressed miR-491-5p inhibited HCC cell proliferation and migration by targeting SEC61 translocon alpha 1 subunit1 (SEC61A) [ 47 ]. The inhibition effect of lenvatinib in sorafenib-resistant HCC cells occurred partially through miRNA regulation.…”