17P Long non-coding RNA SNHG20 promotes non-small cell lung cancer cell progression by silencing of P21 expression

Abstract

Background: Mounting evidence demonstrates that long non-coding RNAs (lncRNAs) are novel transcripts governing multiple biological processes, and that their dysregulation is involved in the development and progression of multiple types of cancer. Small Nucleolar RNA Host Gene 20 (SNHG20) is a 2183 bp lncRNA. The clinical relevance of SNHG20 and its molecular mechanisms involved in non-small cell lung cancer (NSCLC) have not been well documented. Methods: Expression of SNHG20 was analyzed in 42 paired NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Relationship between SNHG20 levels and NSCLC patients clinicopathologic feature was analyzed. Kaplan–Meier survival analysis was used to evaluate the prognosis of patients with high or low SNHG20 expression. Univariate and multivariate survival analysis were performed to further confirm the prognostic role of SNHG20. SNHG20 siRNAs and overexpression vector were transfected into NSCLC cells to knockdown or upregulate SNHG20 expression. In vitro and in vivo studies showed the biological role of SNHG20 in lung cancer cell proliferation and migration. RIP and ChIP assays were carried out to uncover the mechanism of SNHG20's regulation of underlying targets. Results: We found that SNHG20 expression was markedly upregulated in NSCLC tissues, and its upregulation was associated with larger tumor size (P = 0.012), lymph node invasion (P = 0.005) and TNM stage (P = 0.008). Kaplan–Meier survival analysis indicated that patients with low SNHG20 expression level had better progression-free survival (P = 0.003) and overall survival (P = 0.001) than those with high SNHG20 expression. Further univariate and multivariable Cox regression analysis suggested that increased SNHG20 was an independent prognostic indicator for this disease. Knockdown of SNHG20 repressed NSCLC cell proliferation, migration and induced cell apoptosis. Mechanistic investigations revealed that SNHG20 could interact with EZH2, thereby repressing P21 expression. Conclusions: Our findings indicate that SNHG20 is significantly upregulated in NSCLC tissues and it may represent a new candidate for use in NSCLC diagnosis, prognosis and therapy. Legal entity responsible for the study: The Second Affiliated Hospital of Nanjing Medical University Funding: National Natural Science Foundation of China (No. 81472198,81672307); the Key Clinical Medicine Technology Foundation of Jiangsu Province (No. BL2014096); the Medical Innovation Team Foundation of the Jiangsu Provincial Enhancement Health Project (No.21); “333 high class Talented Man Project” (No. BRA2016509) Disclosure: All authors have declared no conflicts of interest.