Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis

Abstract

Background Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. Results In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. Conclusion SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.

circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1

“…(36,37). In HCC, miR-876-5p acts as the targets of LncRNA PITPNA-AS1, long noncoding RNA SNHG14, and LINC-ROR and then regulates proliferation and sorafenib sensitivity of HCC (38)(39)(40). miR-876-5p also suppresses HCC progression by targeting DNMT3A and inhibits EMT and metastasis of HCC by targeting BCL6 corepressor like 1 (BCORL1) (36,41).…”

Long Non-coding RNA Small Nucleolar RNA Host Gene 14, a Promising Biomarker and Therapeutic Target in Malignancy

“…Importantly, the expression level of SNHG14 has been demonstrated correlated with prognosis in patients with NSCLC ( Zhang et al, 2019d ), HCC ( Zhang H. et al, 2020 ), ovarian cancer ( Zhao J. L. et al, 2019 ), retinoblastoma ( Sun et al, 2020 ), pancreatic ductal adenocarcinoma ( Xie et al, 2020 ), colorectal cancer ( Pei et al, 2019 ), cervical cancer ( Ji et al, 2019 ), and endometrial cancer ( Zhao et al, 2020 ). Furthermore, some researchers discovered that highly expressed SNHG14 was positively correlated with large tumor size, advanced TNM stage, distant metastasis and poor tumor differentiation in bladder cancer ( Feng et al, 2021 ), NSCLC ( Zhang et al, 2019d ), HCC ( Liao et al, 2021 ), prostate cancer ( Luo et al, 2020 ), retinoblastoma ( Sun et al, 2020 ), pancreatic cancer ( Deng et al, 2019 ), and cervical cancer ( Ji et al, 2019 ). The results indicate that SNHG14 can become a prognostic indicator of cancers.…”

“…As for biological function, the overexpression of this lncRNA accelerated cell proliferation, invasion, and migration and suppressed cell apoptosis. Conversely, knockdown of SNHG14 could cause the exact opposite effects on HCC cells ( Pu et al, 2019 ; Tang and Yang, 2020 ; Xu X. et al, 2020 ; Zhang H. et al, 2020 ; Liao et al, 2021 ). Mechanistic investigations demonstrated that SNHG14 functions as a competing endogenous RNA and sponged miRNAs, such as miR-4673, miR-217-5p, miR-656-3p, and miR-876-5p ( Pu et al, 2019 ; Tang and Yang, 2020 ; Zhang H. et al, 2020 ; Liao et al, 2021 ).…”

“…Conversely, knockdown of SNHG14 could cause the exact opposite effects on HCC cells ( Pu et al, 2019 ; Tang and Yang, 2020 ; Xu X. et al, 2020 ; Zhang H. et al, 2020 ; Liao et al, 2021 ). Mechanistic investigations demonstrated that SNHG14 functions as a competing endogenous RNA and sponged miRNAs, such as miR-4673, miR-217-5p, miR-656-3p, and miR-876-5p ( Pu et al, 2019 ; Tang and Yang, 2020 ; Zhang H. et al, 2020 ; Liao et al, 2021 ). Thus, activating downstream gene expression, such as, SOCS1, SIRT5, and SSR2 ( Figure 2 ; Pu et al, 2019 ; Tang and Yang, 2020 ; Liao et al, 2021 ).…”

“…Mechanistic investigations demonstrated that SNHG14 functions as a competing endogenous RNA and sponged miRNAs, such as miR-4673, miR-217-5p, miR-656-3p, and miR-876-5p ( Pu et al, 2019 ; Tang and Yang, 2020 ; Zhang H. et al, 2020 ; Liao et al, 2021 ). Thus, activating downstream gene expression, such as, SOCS1, SIRT5, and SSR2 ( Figure 2 ; Pu et al, 2019 ; Tang and Yang, 2020 ; Liao et al, 2021 ). Another research group reported that SNHG14 contributed to tumor cell malignant cells by increasing poly(A) binding protein cytoplasmic 1 (PABPC1) expression through H3K27 acetylation.…”