LncRNA SNHG16 Promotes Hepatocellular Carcinoma Proliferation, Migration and Invasion by Regulating miR-186 Expression

Abstract

Long non-coding RNA (lncRNA) and microRNA (miRNA) play an important role in genesis and progression of tumors. The aim of this study was to explore the expression, biological function and molecular mechanism of small nucleolar RNA host gene 16 (SNHG16) in HCC. RT-qPCR was conducted to evaluate the expression level of SNHG16 in HCC tissues and cell lines. Our findings showed for the first time that SNHG16 was up-regulated in HCC tissues and cell lines. The expression of SNHG16 in cancer tissues was highly correlated with tumor size, TNM stage, ALT expression level and HBV DNA level. Moreover, cell proliferation, migration and invasion were detected by CCK-8 assay, transwell migration assay and transwell invasion assay, respectively. Xenograft tumor experiment was used to determine the biological function of SNHG16 in vivo . As revealed by our data, SNHG16 accelerated the proliferation, migration and invasion of HCC cell. SNHG16 facilitated tumor formation in vivo . Next, the relationship between SNHG16, miR-186 and ROCK1 were analyzed using bioinformatics analysis, qRT-PCR, luciferase reporter assay and western blot. Further molecular mechanism studies reported that the expression of SNHG16 was negatively correlated with the level of miR-186 and SNHG16 directly bound to miR-186. SNHG16 and miR-186 repressed each other. Notably, rescue experiments were conducted and showed that miR-186 reversed the effect of SNHG16 on cell. Taken together, SNHG16 promoted HCC cell proliferation, migration and invasion by functioning as a competitive endogenous RNA (ceRNA) to negatively regulate miR-186 expression. Our data suggested that SNHG16 might be a potential biomarker and a new therapeutic target for HCC.

Construction and Analysis of lncRNA-mediated ceRNA Network in Nasopharyngeal Carcinoma Based on Weighted Correlation Network Analysis

“…Results showed that SNHG16, SNHG17 and THAP9-AS1 were up-regulated in the high-risk group of NPC, while ZNF667-AS1 was down-regulated in the high-risk group of NPC. SNHG16 was regarded as an oncogene and associated with neuroblastoma, bladder cancer, colorectal cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma [50][51][52]. Zhang et al suggested that SNHG16 promotes tumor progression through acting as an endogenous "sponge" by competing with miR-140-5p, thereby regulating target ZEB1 [51].…”

<p><em>SNHG16</em>: A Novel Long-Non Coding RNA in Human Cancers</p>

“…It has been shown that SNHG16 expression is significantly upregulated in tumor tissues and cell lines, such as hepatocellular carcinoma (HCC), lung cancer (LC), colorectal cancer (CRC) and glioma. 15,17,30,31 In addition, overexpression of SNHG16 indicates poor prognosis and is usually correlated with tumor size, lymph node metastasis, tumor grade, disease-free survival, and overall survival (OS). For example, to gain more in-depth knowledge of tumor biology, nine co-expression modules were identified in the Cancer Genome Atlas database after screening and analysis.…”

“…15,[18][19][20][21][22][23] Further analysis showed that high expression of SNHG16 is associated with high tumor grade, multiple tumors, macrovascular invasion, large tumor size, and lymph node status, as well as poor diseasefree survival and shorter overall survival. 15,[19][20][21]23 In HCC patients, multivariate analysis identified SNHG16 overexpression as a significant independent predictor of poor prognosis. 20,23 Moreover, there are other studies of SNHG16 and related clinical effects in non-small cell lung cancer (NSCLC), osteosarcoma, glioma, bladder cancer (BC), ovarian cancer (OC), pancreatic cancer (PC), and papillary thyroid cancer (PTC).…”

“…12 The SNHG16 was initially discovered in neuroblastoma. 13 The dysregulation of SNHG16 has been detected in various types of cancer, including colorectal cancer (CRC), 14 hepatocellular carcinoma (HCC), 15 osteosarcoma, 16 and glioma. 17 Recent studies have demonstrated that SNHG16 expression is upregulated in multiple types of tumors.…”

“…17 Recent studies have demonstrated that SNHG16 expression is upregulated in multiple types of tumors. Furthermore, downregulation of SNHG16 in cancer cells inhibits cell proliferation, invasion, and migration; induces apoptosis; and results in decreased N-cadherin and increased E-cadherin, 15,[18][19][20][21][22][23] suggesting that SNHG16 also acts as an oncogenic lncRNA in cancer.…”