Long non‑coding RNA SNHG17 promotes lung adenocarcinoma progression by targeting the microRNA‑193a‑5p/NETO2 axis

Abstract

Long non-coding RNAs (lncRNAs) play vital roles in human cancers. It has been reported that lncRNA SNHG17 expression is dysregulated in different types of cancer and involved in cancer progression. However, the role of SNHG17 in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to investigate the role of SNHG17 in LUAD. Reverse transcription-quantitative (RT-q) PCR analysis was performed to detect SNHG17 expression in LUAD tissues and cells. The effects of SNHG17 on cancer cell migration, invasion, proliferation and epithelial-to-mesenchymal transition (EMT) were assessed via Transwell, MTT and western blot assays, respectively. The interactions between SNHG17 and microRNA (miRNA/miR)-193a-5p, miR-193a-5p and neuropilin and tolloid-like 2 (NETO2) were assessed via the dual-luciferase reporter assay. NETO2 expression and its potential role in LUAD were analyzed via RT-qPCR analysis and the UALCAN database. The results demonstrated that SNHG17 expression was significantly upregulated in LUAD tissues and cells, and high SNHG17 expression was associated with tumor-node-metastasis stage and poor prognosis of patients with LUAD. SNHG17 knockdown inhibited cell migration, invasion, proliferation and the EMT process. In addition, the results revealed that SNHG17 functions as a competing endogenous RNA of miR-193a-5p. The results of the dual-luciferase reporter assay confirmed that miR-193a-5p can directly target SNHG17. NETO2 was also predicted as a target protein of miR-193a-5p, which was confirmed via the dual-luciferase reporter assay. The roles of NETO2 knockdown in cancer cells were rescued following transfection with miR-193a-5p inhibitor or overexpression of SNHG17. Notably, high NETO2 expression was associated with poor prognosis of patients with LUAD. Bioinformatics analysis demonstrated that the promoter methylation level of NETO2 decreased in LUAD. Taken together, the results of the present study suggest that SNHG17 expression is upregulated in LUAD tissues and cells, and SNHG17 exerts tumor promoting effect by targeting the miR-193a-5p/NETO2 axis.

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

“…STAT3 and transforming growth factor-β (TGF-β) are located upstream of SNHG17, which contribute to activate the PI3K/AKT signaling pathway by increasing SNHG17 levels ( 28 , 29 ). In addition, SNHG17 may indirectly activate the PI3K/AKT signaling pathway through its regulatory effects on NETO2 and PES1 ( 26 , 30 – 32 ).…”

“…Unlocking phenotypic plasticity is mainly manifested by blocking normal cell differentiation in developmental lineages. Notably, as cell development-related transcription factors involved in this process, SOX2, SOX4, and homeobox A1 (HOXA1) can be regulated by SNHG17 ( 3 , 30 , 39 , 62 , 88 ).…”

Integrative Analysis and Experimental Validation Indicated That SNHG17 Is a Prognostic Marker in Prostate Cancer and a Modulator of the Tumor Microenvironment via a Competitive Endogenous RNA Regulatory Network

“…It has been widely recognized that SNGH17 functions as an oncogene in many cancers, such as non-small-cell lung cancer (NSCLC) [ 32 ], breast cancer (BC) [ 33 ], gastric cancer (GC) [ 23 ], and renal cell carcinoma (RCC) [ 34 ]. The tumorigenesis function and related mechanisms of SNHG17 in driving prostate cancer have also been studied.…”

“…Additionally, we observed that the expression of SNHG17, UBE2M, and OTUB1 was significantly correlated with a decreased infiltrating level of immune cells, indicating the immunological role of SNHG17 and its ceRNA regulatory network in prostate cancer. It has been widely recognized that SNGH17 functions as an oncogene in many cancers, such as non-small-cell lung cancer (NSCLC) [32], breast cancer (BC) [33], gastric cancer (GC) [23], and renal cell carcinoma (RCC) [34]. The tumorigenesis function and related mechanisms of SNHG17 in driving prostate cancer have also been studied.…”

Comprehensive Analysis of NPSR1-AS1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma

“…For instance, Zhang et al indicated that the expressions of SNHG17 were highly elevated in LUAD specimens and cells, and high SNHG17 expression was related to advanced stages of tumor node metastases and a bad prognosis for patients who had LUAD. The targeting of the microRNA-193a-5p/NETO2 axis by SNHG17 knockdown resulted in an inhibition of the EMT process as well as cell migration, invasion, and proliferation [ 19 ]. Cong et al showed that it is possible that the lncRNA known as linc00665, which was found to be significantly overexpressed in lung adenocarcinoma (LUAD) tissues, can act as an independent predictor of a bad prognosis.…”