LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma

Abstract

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines. The effect of SNHG17 on proliferation, migration, and apoptosis of HCC was investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets, and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion, and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation and migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation, and apoptotic pathway; among them, 92 were overlapped with SNHG17-related genes in the TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2, and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival, and ERH and PDK4 also played a marked role in the prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.

Enabling factor for cancer hallmark acquisition: Small nucleolar RNA host gene 17

“…Concerning the studies on the relationship between SNHG17 and tumors, the most significant relationship is the promotion of tumor proliferation, invasion, and metastasis. Several studies have shown that the high-level expression of SNHG7 correlates with lymph node metastasis, distant metastasis, and tumor invasion depth in various tumors ( 19 , 29 , 42 , 44 , 46 ). Spreading to distant organs is recognized to be the most prominent hallmark of cancer cells.…”

“…Thus, targeting SNHG17 may become a promising strategy for tumor therapy. In addition, SNHG17 can be an independent prognostic factor in hepatocellular carcinoma, renal cell carcinoma, colorectal cancer, gastric cancer, and melanoma ( 26 , 28 , 44 , 46 , 103 ) and a diagnostic predictor in cervical and gastric cancers ( 19 , 42 ) ( Table 1 ). Therefore, SNHG17 is an emerging biomarker for cancer diagnosis and prognosis.…”

“…Thus, resistance to apoptosis is a barrier that must be breached for tumor formation. The anti-apoptotic effect of SNHG17 on tumor cells has been currently observed in a variety of tumors, including cervical cancer, pancreatic cancer, astrocytoma, hepatocellular carcinoma, oral squamous cell carcinoma, prostate cancer, ovarian cancer, gastric cancer, melanoma, and colorectal cancer (15,16,19,23,28,39,(42)(43)(44)(45). This anti-apoptotic mechanism was associated with increased anti-apoptotic protein Bcl-2 and the decreased activity of the pro-apoptotic proteins caspase3, caspase8, caspase9, and Bax (33,35,36,40,46,47).…”

Long noncoding RNA SNHG17: a novel molecule in human cancers

“…This discrepancy is likely related to a high burden of chronic hepatitis in China [ 58 ]. Several studies previously assessed levels of SNHG17 in human HCCs and adjacent normal tissues via qRT-PCR [ 16 , 59 , 60 ] and found a significant upregulation of SNHG17 in cancer tissues. Ma et al [ 16 ] showed that overexpressed SNHG17 promoted the proliferation, migration, invasion and EMT progression of HCC cells.…”

Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials

“…LncRNA-hPVT1, AFAP1-AS1, XIST, HOXA cluster antisense RNA 2 (HOXA-AS2), HOST2, and cervical carcinoma high-expressed lncRNA 1 (CCHE1) are examples of lncRNAs that can cause and promote cell proliferation, suppressing apoptosis of HCC cells [ 28 , 176 ]. LncRNA SNHG17 is considerably upregulated in tissues and cell lines of HCC and associated with large tumor size, poor differentiation, and the presence of vascular invasion [ 177 ]. The lncRNA TUG1-miR328-3p-SRSF9 mRNA axis works as a unique ceRNA regulator axis related to HCC malignancies [ 178 ].…”