Dataset Information

Circular RNA ZNF609 Promoted Hepatocellular Carcinoma Progression by Upregulating PAP2C Expression via Sponging miR-342-3p.

ABSTRACT: Background:Emerging evidence has revealed that circular RNAs (circRNAs) participated in hepatocellular carcinoma (HCC) development. However, the roles of most circRNAs have not been studied. Methods:CircZNF609, miR-342-3p and RAP2C expressions were assessed by qPCR or Western blot. Loss-of-function experiments were performed using si-circZNF609 transfection, followed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Informatic tools and rescue experiments were carried out to investigate the underlying mechanisms. Results:We showed that circZNF609 was overexpressed in HCC tissues and cells, as well as associated with poor clinical characteristics. Depletion of circZNF609 restrained HCC cell viability, migration and invasion while enhanced cell apoptosis. As to mechanism, miR-342-3p was sponged by circZNF609, and RAP2C was targeted by miR-342-3p. The effects on HCC cells induced by si-circZNF609 could be reversed by miR-342-3p inhibitor or RAP2C. In vivo, circZNF609 knockdown inhibited tumorigenesis of HCC mice, confirming the findings in vitro. Conclusion:CircZNF609 was highly expressed in HCC tissues and driven HCC progression by sponging miR-342-3p and upregulating RAP2C. This study may provide new potential therapeutic targets for HCC treatment.

SUBMITTER: Liao X

PROVIDER: S-EPMC7414977 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA ZNF609 Promoted Hepatocellular Carcinoma Progression by Upregulating PAP2C Expression via Sponging miR-342-3p.

Liao Xin X Zhan Wei W Tian Bin B Luo Yilin Y Gu Fang F Li Rui R

OncoTargets and therapy 20200804

<h4>Background</h4>Emerging evidence has revealed that circular RNAs (circRNAs) participated in hepatocellular carcinoma (HCC) development. However, the roles of most circRNAs have not been studied.<h4>Methods</h4>CircZNF609, miR-342-3p and RAP2C expressions were assessed by qPCR or Western blot. Loss-of-function experiments were performed using si-circZNF609 transfection, followed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Informatic tools and rescue experiments we ...[more]

PMID: 32801783

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Project description:As a recently discovered noncoding RNA, circular RNAs (circRNAs) have been identified to play key roles in cancer biology; however, the detailed functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unclarified. RNA-seq analysis was used to screen the expression profiles of circRNAs in HCC. CircZNF566 expression in HCC tissues and cell lines was detected by qRT-PCR. In vitro CCK-8, colony formation, wound healing, transwell migration, and invasion assays and in vivo tumorigenesis and metastasis assays were conducted to determine the functions of circZNF566. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed to confirm the relationship between circZNF566 and miR-4738-3p. Bioinformatics analysis and luciferase reporter assays were employed to determine whether miR-4738-3p regulates tryptophan 2,3-dioxygenase (TDO2) expression. Finally, immunohistochemistry (IHC) was used to detect the level of TDO2 and determine its prognostic value. CircZNF566 was significantly upregulated in HCC tissues and cell lines. High circZNF566 expression in HCC tissues was positively correlated with clinicopathological features and poor prognosis. Functionally, in vitro experiments showed that circZNF566 promoted HCC cell migration, invasion, and proliferation, whereas in vivo experiments showed that circZNF566 promoted tumorigenesis and metastasis. Mechanistically, circZNF566 acted as a miR-4738-3p sponge to relieve the repressive effect of miR-4738-3p on its target TDO2. In addition, miR-4738-3p suppressed HCC cell migration, invasion, and proliferation, while TDO2 was positively correlated with pathological features and poor prognosis and promoted cell migration, invasion, and proliferation in HCC. CircZNF566 is a novel tumor promoter in HCC and functions through the circZNF566/ miR-4738-3p /TDO2 axis; in addition, circZNF566 may serve as a novel diagnostic marker, prognostic indicator, and target for the treatment of HCC.

Project description:BackgroundHepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear.MethodsqRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18.ResultscircTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression.ConclusionOur data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment.

Dataset Information

Circular RNA ZNF609 Promoted Hepatocellular Carcinoma Progression by Upregulating PAP2C Expression via Sponging miR-342-3p.

Publications

Circular RNA ZNF609 Promoted Hepatocellular Carcinoma Progression by Upregulating PAP2C Expression via Sponging miR-342-3p.

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