Circular RNA circSP3 promotes hepatocellular carcinoma growth by sponging microRNA-198 and upregulating cyclin-dependent kinase 4.
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ABSTRACT:
SUBMITTER: Li M
PROVIDER: S-EPMC8351711 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this study, we investigated the mechanistic role of the long non-coding RNA (lncRNA) AC092171.4 in hepatocellular carcinoma (HCC). AC092171.4 was significantly upregulated in HCC tumor tissues compared to normal liver tissues. HCC patients with high AC092171.4 expression showed poorer overall survival (OS) and disease-free survival (DFS) than those with low AC092171.4 expression. In vitro cell proliferation, migration and invasiveness were all higher in AC092171.4-overexpressing HCC cells, but lower in AC092171.4-silenced HCC cells, than in controls. Balb/c nude mice injected with AC092171.4-silenced HCC cells had smaller xenograft tumors, which showed less growth and pulmonary metastasis than control tumors. Bioinformatics analyses and dual luciferase reporter assays confirmed that AC092171.4 binds directly to miR-1271, which targets the 3'UTR of GRB2 mRNA. AC092171.4 expression correlates negatively with miR1271 expression and correlates positively with GRB2 mRNA expression in HCC tissues from patients. HCC cells co-transfected with miR-1271 mimics and sh-AC092171.4 show less proliferation, migration, invasiveness, GRB2 protein, and epithelial to mesencyhmal transition (EMT) than sh-AC092171.4-transfected HCC cells. These findings demonstrate that AC092171.4 promotes growth and progression of HCC by sponging miR-1271 and upregulating GRB2. This makes AC092171.4 a potential prognostic indicator and therapeutic target for HCC patients.
| S-EPMC7425487 | biostudies-literature
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.
| S-EPMC7938576 | biostudies-literature
Project description: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.
| S-EPMC7414977 | biostudies-literature
Project description:CircRNAs participate in the pathogenesis of a variety of cancers. Previous studies showed that baculoviral IAP repeat containing 5 (BIRC5) can promote tumor progression. But, the mechanisms by which circRNAs regulate BIRC5 expression in hepatocellular carcinoma (HCC) remain unknown. The clinical prognosis of BIRC5 or miR-497-5p expression in patients with HCC was assessed by TCGA RNA-seq dataset. hsa_circ_0026939 (circANKRD52) or BIRC5 was identified to bind with miR-497-5p by luciferase gene report, RIP and circRIP assays. MTT, colony formation, Transwell assays and a xenograft tumor model were used to estimate the role of miR-497-5p or circANKRD52 in HCC cells. As a result, we found that elevated expression of BIRC5 or decreased expression of miR-497-5p was linked to poor survival in HCC. Restored expression of miR-497-5p repressed cell proliferation, colony formation and invasiveness by targeting BIRC5, but its inhibitor showed the opposite results. Furthermore, circANKRD52 possessed a tumor-promoting effect by acting as a sponge of miR-497-5p and thereby upregulated BIRC5 in HCC cells. In conclusion, our findings demonstrated that circANKRD52 enhances the tumorigenesis of HCC by sponging miR-497-5p and upregulating BIRC5 expression.
| S-EPMC8058805 | biostudies-literature
Project description:Accumulating evidence has demonstrated the roles of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC); however, their roles in HCC need to be further studied. Through high-throughput human circRNA microarray analysis of HCC and adjacent normal tissues, we identified hsa_circ_0051040 as a novel candidate circRNA for the diagnosis and treatment of HCC. In this study, we found that hsa_circ_0051040 was overexpressed in HCC tissues and cell lines and that its expression was correlated with poor prognosis. Knockdown of hsa_circ_0051040 inhibited the migration, invasion, and proliferation of HCC cells in vitro and in vivo, whereas overexpression of hsa_circ_0051040 had the opposite effects. Moreover, our data demonstrated that hsa_circ_0051040 acted as a sponge for miR-569 to regulate ITGAV expression and induce EMT progression. Our findings indicated that hsa_circ_0051040 promotes HCC development and progression by sponging miR-569 to increase ITGAV expression. Thus, hsa_circ_0051040 is a good candidate as a therapeutic target.
| S-EPMC9688127 | biostudies-literature
Project description:Circular RNA (circRNA) features prominently in the progression of hepatocellular carcinoma (HCC), of which the biological function and potential mechanism of circ_0008274 in HCC are obscure. The present study aims to explore circ_ 0008274's biological functions and underlying mechanisms in HCC. The expressions of circ_0008274, miR-140-3p and Granulin (GRN) mRNA in HCC tissues and cells were investigated by quantitative real-time polymerase chain reaction. Besides, GRN protein expression was measured by Western blot. Furthermore, chi-square test was used to probe the interrelation between circ_0008274 expression and clinicopathological parameters. In addition, cell counting kit-8 (CCK-8) and EdU assays were applied to detect cell proliferation. Moreover, transwell assay was used to detect cell migration and invasion. What's more, bioinformatics prediction, dual-luciferase reporter gene assay and RNA Immunoprecipitation experiments were used to corroborate the targeting interrelations among circ_0008274, miR-140-3p and GRN. Herein we reported that circ_0008274 was highly expressed in HCC, and its high expression enhanced the proliferation, migration, and invasion of HCC cells, while depleting circ_0008274 inhibited the malignant biological behaviors of HCC cells. Mechanistically, circ_0008274 upregulates GRN expressions via adsorbing miR-140-3p to expedite the progression of HCC.
| S-EPMC8806606 | biostudies-literature
Project description:Background/aims:The dysregulation of circABCB10 may play an critical role in tumor progression. However, its function in liver cancer (HCC) is still unclear. Therefore, this experimental design is based on circABCB10 to explore the pathogenesis of HCC. Methods:The expression of circABCB10 and miR-670-3p in HCC tissues was detected by RT-qPCR. CCK-8, Brdu incorporation, colony formation and transwell assays were used to determine the effect of circABCB10 on HCC cell proliferation and migration. Target gene prediction and screening, luciferase reporter assays were used to validate downstream target genes of circABCB10 and miR-670-3p. HMG20A expression was detected by RT-qPCR and Western blotting. The tumor changes in mice were detected by in nude mice. Results:CircABCB10 was significantly increased in HCC tissues and cell lines, and high CircABCB10 expression was directly associated with low survival in HCC patients. Silencing of circABCB10 inhibited proliferation and invasion of hepatocellular carcinoma. In addition, circABCB10 acted as a sponge of miR-670-3p to upregulate HMG20A expression. In addition, overexpression of miR-670-3p or knockdown of HMG20A reversed the carcinogenic effects of circABCB10 in HCC. There was a negative correlation between the expression of circABCB10 and miR-670-3p, and a positive correlation between the expression of circABCB10 and HMG20A in HCC tissues. Conclusion:circABCB10 promoted HCC progression by modulating the miR-670-3p/HMG20A axis, and circABCB10 may be a potential therapeutic target for HCC.Trail registration JL1H384739, registered at Sep 09, 2014.
| S-EPMC6915995 | biostudies-literature
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.
| S-EPMC7293356 | biostudies-literature
Project description:BackgroundCancer metastasis is responsible for 90% of cancer-related deaths. Recently, circular RNA (circRNA) is deemed to be an important regulator of cancer progression. However, little is known about the role of circRNA in the metastasis of lung adenocarcinoma (LUAD). Herein, we investigated the clinical implication and regulatory effect of circ-TSPAN4 (hsa_circ_0020732) in LUAD.MethodsGene Expression Omnibus (GEO) database (GSE104854) was used to identify the aberrantly expressed circRNAs in LUAD. The expression levels of circ-TSPAN4, miR-4731-5p, miR-665, and ZEB1 were determined by quantitative reverse transcription PCR (qRT-PCR). The functional experiments were carried out with wound healing and transwell assays. And, the luciferase reporter and RNA pull-down assays were employed to examine the crosstalk between circ-TSPAN4, miR-665, and ZEB1. In vivo metastasis experiment was tested by the lung metastasis model.ResultsCirc-TSPAN4 was significantly upregulated in LUAD tissues and cell lines. The increased circ-TSPAN4 was linked to advanced tumor-node-metastasis stage, lymph node and distant metastasis, and poor outcome. Lentivirus-mediated stably circ-TSPAN4 knockdown dramatically attenuated the metastatic ability of LUAD cells both in vitro and in vivo. Mechanistically, circ-TSPAN4 directly interacted with miR-665, but not miR-4731-5p, to increase the expression of ZEB1, which is a well-known metastasis trigger. Importantly, the reduced metastatic capacity caused by circ-TSPAN4 depletion was partially rescued by miR-665 silencing or ZEB1 overexpression.ConclusionsCirc-TSPAN4 plays a pivotal metastasis-promoting role in LUAD through acting as a sponge for miR-665 and upregulating ZEB1.
| S-EPMC6900391 | biostudies-literature
Project description:BackgroundMost of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered.MethodsIn this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo.ResultsWe found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells.ConclusionsOur findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.
| S-EPMC8335894 | biostudies-literature