Abstract
ObjectiveThe purpose of the study is to explore the potential competing endogenous RNA (ceRNA) network and investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in hepatocellular carcinoma (HCC) development.MethodsBy analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed lncRNA and microRNA (miRNA) profiles and constructed ceRNA networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of SNHG1 and LMNB2 on tumor proliferation and growth in vitro and in vivo.ResultsIn the study, we identified 115 messenger RNAs (mRNAs), 12 lncRNAs, and 37 miRNAs by intersecting differentially expressed genes (DEGs) in TCGA and StarBase databases. Then, SNHG1–miR-326–LMNB2 pathway came into notice after further survival analysis and hub gene screening. Our results showed that SNHG1 expression was upregulated significantly in HCC tissues and cell lines. Downregulation of both LMNB2, the target of miR-326 in HCC, and SNHG1 inhibited tumor proliferation and growth in vitro and in vivo. Furthermore, SNHG1 could regulate LMNB2 expression through binding to miR-326 in HCC cell lines.Conclusion SNHG1 is a promising prognostic factor in HCC, and the SNHG1–miR-326–LMNB2 axis may be a potential therapeutic target for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide and the sixth leading cause of incident cancer cases [1, 2]
By analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed Long noncoding RNAs (lncRNAs) and microRNA profiles and constructed competing endogenous RNA (ceRNA) networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of small nucleolar RNA host gene 1 (SNHG1) and LMNB2 on tumor proliferation and growth in vitro and in vivo
Our results showed that SNHG1 expression was upregulated significantly in HCC tissues and cell lines
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide and the sixth leading cause of incident cancer cases [1, 2]. HCC is a highly heterogeneous tumor that may be the main cause of treatment failure, so the biological diversity of HCC poses a considerable challenge for individualized therapy [5, 6]. It is urgent to explore the molecular mechanism of tumor progression and identify novel therapeutic targets for HCC. LncRNAs acted as a competing endogenous RNA (ceRNA) and bound with specific microRNA (miRNA), regulating the corresponding downstream messenger RNA (mRNA) translation [12–14]. SNHG1 has been reported to function as an oncogene through sponging miR-195-5p [15], miR-377-3p [16], and miR-195 [17] in HCC, in the present study, we made use of The Cancer Genome Atlas (TCGA) database and identified a novel molecular mechanism of SNHG1 in HCC growth
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