CircC16orf62 promotes hepatocellular carcinoma progression through the miR-138-5p/PTK2/AKT axis.
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ABSTRACT:
SUBMITTER: Zhang S
PROVIDER: S-EPMC8190090 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAberrant 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.MethodsQuantitative 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.ResultsIn 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.ConclusionSNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.
| S-EPMC7824933 | biostudies-literature
Project description:To explore the role of long-chain non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in the development of colorectal cancer (CRC) via the miR-138-5p/zinc finger E-box-binding homeobox 2 (ZEB2) axis. Eighty-four CRC tissue specimens and 84 corresponding paracancerous tissue specimens were sampled from 84 patients with CRC admitted to the First Hospital of Jilin University from January 2018 to September 2019. The TUG1 expression in the specimens was determined, and its value in diagnosis and prognosis of CRC was analyzed. Additionally, constructed stable and transient overexpresison vectors and inhibition vectors were transfected into CRC cells. The MTT, transwell, and flow cytometry were adopted for analysis on the proliferation, invasion, and apoptosis of transfected cells, respectively, and a dual luciferase reporter (DLR) assay was carried out for correlation determination between TUG1 and miR-138-5p and between miR-138-5p and ZEB2. TUG1 was up-regulated in CRC, and serum TUG1 could be adopted as a diagnostic marker of CRC, with area-under-the-curve (AUC) larger than 0.8. In addition, siRNA-TUG1, shRNA-TUG1, miR-138-5p-mimics, and miR-138-5p-inhibitor were transfected into cells, and it turned out that overexpressing miR-138-5p and inhibiting ZEB2 exerted the same effects. The DLR assay revealed that TUG1 was able to targetedly regulate miR-138-5p, and miR-138-5p could targetedly regulate ZEB2, and in vitro experiments revealed that TUG1 could affect the epithelial-to-mesenchymal transition (EMT) of CRC via the miR-138-5p/ZEB2 axis. TUG1 could promote the development of CRC via the miR-138-5p/ZEB2 axis.
| S-EPMC7280475 | biostudies-literature
Project description:BackgroundHigh frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.MethodsReal-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.ResultsWe showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.ConclusionsConsistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.
| S-EPMC5782375 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) were reported to be involved in the progression of a variety of cancers, including colorectal cancer (CRC). However, the precise functions and mechanism of circRNAs in CRC have not been elucidated. This study aimed to investigate the effect and mechanism underlying circ_0006174 in CRC.MethodsThe expression of circ_0006174, microRNA (miR-138-5p) and metastasis associated in colon cancer 1 (MACC1) mRNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR) assay. Western blot was employed to measure MACC1 protein expression. The effects of circ_0006174 knockdown, MACC1 overexpression or miR-138-5p inhibition on cell proliferation, migration, invasion, and apoptosis were assessed by cell counting kit 8 (CCK-8) assay, clone formation assay, transwell assay and flow cytometry assay, respectively. The interaction between miR-138-5p and circ_0006174 or MACC1 was confirmed by RNA pull down assay or dual-luciferase reporter assay. Xenograft tumor model in nude mice was used to verify the function of circ_0006174 in vivo.ResultsCirc_0006174 and MACC1 expression was highly expressed, while miR-138-5p expression was downregulated in CRC cells and tissues. Meanwhile, circ_0006174 functioned as a sponge of miR-138-5p to upregulate MACC1 expression. Furthermore, circ_0006174 knock down-mediated suppression on cell proliferation, migration and invasion, and promotion on cell apoptosis could be alleviated by MACC1 overexpression or miR-138-5p inhibition in CRC cells. Besides, circ_0006174 knockdown also inhibited CRC procession in vivo.ConclusionCirc_0006174 advanced CRC progression via sponging miR-138-5p to upregulate MACC1 expression, which may provide a promising molecular target for CRC treatment.
| S-EPMC7899310 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.MethodsThe expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.ResultsCircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.ConclusionsCircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.
| S-EPMC7735421 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT-related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up-regulating the expression of MAP3K2 via sponging miR-1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.
| S-EPMC7810943 | biostudies-literature
Project description:Background and objectivesThe roles of microRNA(miR)-106b-5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR-106b-5p expression in HCC and its underlying mechanisms.MethodsExpression levels of miR-106b-5p in 108 HCC clinical samples by quantitative real-time reverse transcription PCR. Associations of miR-106b-5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi-square test, Kaplan-Meier, and Cox proportional regression analyses, respectively. The target gene of miR-106b-5p and their functions in HCC cells were investigated by luciferase reporter, CCK-8, and Transwell Matrigel invasion assays.ResultsmiR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals. Importantly, miR-106b-5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR-106b-5p in HCC cells. Functionally, miR-106b-5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR-106b-5p overexpression.ConclusionsmiR-106b-5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR-106b-5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.
| S-EPMC6825988 | biostudies-literature
Project description:CircRNA/miRNA/mRNA axis has been reported to play crucial regulatory roles in multiple cancers, including hepatocellular carcinoma (HCC). In addition, recent investigations revealed that aloin exerted anti-tumor functions in HCC. However, the underlying mechanism of aloin on anti-tumor functions in HCC remained elusive. Therefore, this study aimed to investigate whether circRNA/miRNA/mRNA axis medicated the anti-tumor effect of aloin in HCC. Cell viability, invasion, apoptosis and autophagy were accessed by cell counting kit-8 (CCK-8), transwell invasion assay, flow cytometry, Western blot and immunofluorescence analysis, respectively. Expression levels of circ_0011385, miR-149-5p and WT1 mRNA were determined using qRT-PCR assay. Binding sites between miR-149-5p and circ_0011385 or WT1 were predicted in starBase database. The binding relationship among circ_0011385, miR-149-5p and WT1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation. Besides, the rescue experiments were performed by co-transfection with cric_0011385 overexpression plasmid, si-cric_0011385, miR-149-5p mimic and inhibitor, WT1 pDNA and si-WT1 in HCC cells. Furthermore, tumor growth was also investigated in the xenograft mouse model. Aloin inhibited HCC proliferation and invasion as well as promoted apoptosis and autophagy both in vitro and in vivo. Besides, aloin suppressed circ_0011385 expression. Overexpressed circ_0011385 partially reversed the anti-tumor effect of aloin on HCC. In addition, it was revealed that the circ_0011385, miR-149-5p and WT1 genes were abnormally expressed in HCC. Furthermore, the binding interactions between circ_0011385, miR-149-5p and WT1 were predicted and confirmed. Moreover, the effect of circ_0011385 on the anti-tumor role of aloin in HCC was rescued by miR-149-5p mimics. MiR-149-5p regulated HCC progression via modulating WT1. Aloin suppressed cell proliferation, invasion and tumor growth and promoted apoptosis and autophagy in HCC through regulating circ_0011385/miR-149-5p/WT1 axis. Aloin may be a potential candidate drug for HCC treatment.Abbrevations: HCC: Hepatocellular carcinoma; ceRNA: competing endogenous RNA; miRNA: microRNA; MREs: miRNA response elements; WT1: Wilms' tumor 1; MMP-2: Matrix metalloproteinase; EMT: epithelial-mesenchymal transition; GADPH: glyceraldehyde 3-phosphate dehydrogenase; WT: wild type; MUT: mutant type; DMEM: dulbecco's modified eagle medium.
| S-EPMC8794511 | biostudies-literature
Project description:BACKGROUND:Recent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined. METHODS:Quantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ. Bioinformatics analysis and luciferase reporter assay were utilized to confirmthe binding ofmiR-22 to the 3' untranslated region (3'-UTR) of galectin-9. The methylation status of miR-22 promoter was analyzed by MSP (Methylation specific PCR) and BSP (bisulfite sequencing PCR), while chromatin immunoprecipitation (ChIP) assay identify the occupation status of EZH2 and H3K27me3 at the promoter. Furthermore, the effect of ectopic expression of galectin-9 and miR-22 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, transwell assays and flow cytometric analysis, respectively. RESULTS:IFN-γ induces up-regulation of galectin-9 and EZH2 in HCC cell lines. Galectin-9 is a target of miR-22 and EZH2 facilitates galectin-9 expression by tri-methylation of H3K27 on miR-22 promoter but not hyper-methylation status of DNA. MiR-22 overexpression suppressed HCC cell growth, invasion, and metastasis both in vitro and in vivo. Interestingly, galectin-9 also exhibited antitumor effects, and restoring galectin-9 expression in miR-22 overexpressing cells strengthened its antitumor effects. CONCLUSIONS:These findings indicated that EZH2 facilitates galectin-9 expression by epigenetically repressing miR-22 and that galectin-9, which is known as an immunosuppressant, also functions as a tumor suppressor in HCC.
| S-EPMC5761110 | 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