Has_circ_0008583 modulates hepatocellular carcinoma progression through the miR-1301-3p/METTL3 pathway
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ABSTRACT:
SUBMITTER: Wang F
PROVIDER: S-EPMC8805961 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Hepatocellular carcinoma (HCC) is a common lethal malignant tumor worldwide. Circular RNAs (circRNAs) have been reported to affect the development of human cancers, including HCC. In this project, we aim to clarify the functional effect of circular CDR1as (circ_CDR1as) on HCC progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot is implemented to detect the expression of circ_CDR1as, microRNA (miR)-1287 and Raf-1 proto-oncogene, serine/threonine kinase (Raf1). Cell proliferation is assessed via colony formation and 3-(4, 5)-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide (MTT) assays. Cell migration and invasion are measured by Transwell assay. The target relationship between miR-1287 and circ_CDR1as or Raf1 is validated through dual-luciferase reporter assay. The levels of epithelia–mesenchymal transition (EMT) markers and the MEK/ERK signal pathway-related proteins are examined by Western blot. Model in nude mice is constructed to determine the role of circ_CDR1as in vivo. Results Expression of circ_CDR1as and Raf1 is elevated, while miR-1287 expression is decreased in HCC. Depletion of circ_CDR1as or Raf1 could inhibit proliferation and metastasis of HCC cells. Besides, circ_CDR1as regulates Raf1 expression by targeting miR-1287. MiR-1287 upregulation or Raf1 depletion could partially counterbalance circ_CDR1as depletion-mediated inhibitory effects on HCC cell behaviors. Moreover, circ_CDR1as depletion represses HCC progression through inactivating MEK/ERK pathway. In addition, circ_CDR1as depletion suppresses tumor growth in vivo via regulating miR-1287/Raf1 pathway. Conclusion Circ_CDR1as depletion inhibits HCC cell proliferation and metastasis by miR-1287/Raf1 and MEK/ERK pathways, highlighting a promising molecular target for HCC treatment.
| S-EPMC7522432 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are enriched in exosomes and are extremely stable. Exosome-mediated intercellular transfer of specific biologically active circRNA molecules can drive the transformation of the tumor microenvironment and accelerate or inhibit the local spread and multifocal growth of hepatocellular carcinoma (HCC). In this study, we explored in depth about the biological roles of HCC cell-derived exosomes and exosome-transported circRNAs on HCC in vivo and in vitro.MethodsExosomes extracted from HCC cells (Huh7 and HA22T) were characterized using transmission electron microscopy, nanoparticle size tracer analysis, and western blotting. Exosomes were observed for endocytosis using fluorescent labeling. The effects of HCC cell-derived exosomes and the circ_002136 they carried on cell growth, metastasis and apoptosis were determined by CCK-8 assay, transwell assay, flow cytometry analysis and TUNEL staining, respectively. The expressions of circ_002136, miR-19a-3p and RAB1A were detected by quantitative RT-PCR (qRT-PCR). Targeted binding between miR-19a-3p and circ_002136 or RAB1A was predicted and verified by bioinformatics analysis, dual-luciferase reporter and RNA pull-down experiments. The in vivo effect of circ_002136 was determined by constructing a xenograft tumor model.ResultsThe findings revealed that Huh7 and HA22T exosomes conferred enhanced viability as well as invasive ability to recipient HCC cells. Circ_002136 was shown for the first time to be differentially upregulated in HCC tissues and cells and transferred by HCC cell-derived exosomes. More importantly, selective silencing of circ_002136 depleted the malignant biological behaviors of HCC exosome-activated Huh7 and HA22T cells. Depletion of circ_002136 in vivo effectively retarded the growth of HCC xenograft tumors. Furthermore, a well-established circ_002136 ceRNA regulatory network was constructed, namely circ_002136 blocked miR-19a-3p expression, elevated RAB1A expression activity and stimulated HCC development. Finally, high levels of circ_002136 or RAB1A, as well as low levels of miR-19a-3p, negatively affected HCC patient survival.ConclusionThe study on circ_002136 provides good data to support our insight into the mechanism of to-be-silenced circRNA as a therapeutic agent in the progression of HCC.
| S-EPMC9730599 | biostudies-literature
Project description:ObjectiveAn increasing number of studies have indicated that long noncoding RNAs (lncRNAs) play an important role in the pathogenesis of hepatocellular carcinoma (HCC). In this study, we aimed to clarify the roles of RP11-295G20.2 in HCC progression and the underlying molecular mechanisms.ResultsBioinformatics analyses based TCGA data suggested that RP11-295G20.2 was significantly upregulated in HCC tissues and increased RP11-295G20.2 expression level correlated with poor overall survival of patients with HCC. The results of RT-PCR further showed that RP11-295G20.2 was upregulated in HCC tissues and cell lines. Functionally, RP11-295G20.2 knockdown significantly inhibited the proliferation, colony formation, invasion and migration, but induced the apoptosis of HCC cells. In line with this, downregulation of RP11-295G20.2 in HCC lines markedly suppressed the tumor growth in vivo. Mechanistically, RP11-295G20.2 could upregulate CCNB1 through targeting miR-6884-3p. More importantly, our rescue experiments revealed that miR-6884-3p/CCNB1 axis was involved in RP11-295G20.2-meditated tumorigenic behaviors of HCC cells.ConclusionsRP11-295G20.2 can contribute to HCC progression at least partly via the miR-6884-3p/CCNB1 axis, suggesting that RP11-295G20.2 may be a potential target for HCC therapy.MethodsRT-qPCR was employed to examine the expression levels of RP11-295G20.2, miR-6884-3p, and CCNB1 in HCC tissues and cell lines. CCK8 assay, transwell assay, colony formation assay and flow cytometry analysis were performed to evaluate the biological function of RP11-295G20.2 in HCC cells. The xenograft tumor assay was used to assess the effect of RP11-295G20.2 on the in vivo growth of HCC cells. The luciferase reporter assay, RIP assay and Spearman's correlation analysis were performed to explore the potential mechanisms underlying the roles of RP11-295G20.2 in HCC progression.
| S-EPMC7425504 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is one of the most common cancers with high prevalence and mortality, and it has brought huge economic and health burden for the world. It is urgent to found novel targets for HCC diagnosis and clinical intervention. Circular RNA (circRNA) has been reported to participate in many cancer progressions including HCC, suggesting that circRNA might paly essential role in HCC initiation and progression. Our study aims to found that potential circRNA participates in HCC development and its underlying molecular mechanisms. We obtained three pairs of HCC tissues and its adjacent normal tissues data from GEO DataSets. MTT, cell colony, EdU, wound-healing, transwell invasion and mouse xenograft model assays were used to demonstrate the biological functions of circCAMSAP1 in HCC progression. Furthermore, we conducted bioinformatics analysis, AGO2-RIP, RNA pull-down and luciferase reporter assays to assess the association of circCAMSAP1-miR-1294-GRAMD1A axis in HCC cells. The expression of circCAMSAP1 was up-regulated in HCC tissues compared with its adjacent normal tissues. Up-regulation of circCAMSAP1 promoted HCC biological functions both in vitro and in vivo. The promotive effects of circCAMSAP1 on HCC progression function through miR-1294/GRAMD1A pathway. CircCAMSAP1 was up-regulated in HCC tissues, and circCAMSAP1 up-regulated GRAMD1A expression to promote HCC proliferation, migration and invasion through miR-1294. CircCAMSAP1 might be a potential prognosis and therapeutic target for HCC.
| S-EPMC8051675 | biostudies-literature
Project description:Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of head and neck cancers. In the past decades, although the therapy strategies of LSCC have made considerable improvement, the terrible outcomes of LSCC still bring an enormous burden to the world health care system. Novel therapeutic targets for LSCC are urgently needed. lncRNAs exert important roles in various biological progressions, including LSCC. Here, we aimed to investigate the function of lncRNA PVT1 in LSCC progression and its underlying molecular mechanisms. By conducting multiple experiments, our results showed that lncRNA PVT1 was upregulated in LSCC cell lines and regulated LSCC cell proliferation, apoptosis, and its cell susceptibility to natural killer (NK) cells. Moreover, it was found that lncRNA PVT1 promotes MBNL1 expression to regulate LSCC cellular progression through sponging miR-1301-3p. Our study might provide novel targets for LSCC basic research or clinical management.
| S-EPMC8604577 | biostudies-literature
Project description:Circular RNAs (circRNAs) have confirmed to participate in diverse biological functions in cancer. However, the expression patterns of circRNAs on hepatocellular carcinoma (HCC) remains unclear. In the present study, we clarified that hsa_circRNA_104348 was dramatically upregulated in HCC tissues and cells. Patients with HCC displaying high hsa_circRNA_104348 level possessed poor prognosis. Has_circ_104348 facilitated proliferation, migration, and invasion, meanwhile suppressed apoptosis of HCC cell. Furthermore, hsa_circRNA_104348 directly targeted miR-187-3p, could regulate miR-187-3p to affect proliferation, migration, invasion, and apoptosis of HCC cells, and may have effect on Wnt/β-catenin signaling pathway. Moreover, RTKN2 could be a direct target of miR-187-3p. In addition, knockdown of hsa_circRNA_104348 attenuated HCC tumorigenesis and lung metastasis in vivo. Taken together, these findings indicated that circular RNA hsa_circRNA_104348 might function as a competing endogenous RNA (ceRNA) to promotes HCC progression by targeting miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway.
| S-EPMC7734058 | biostudies-literature
Project description:Recent studies have shown that miR-494-3p is oncogene and has a central role in many solid tumors; however, the role of miR-494-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, it was found that miR-494-3p was up-regulated in HCC tissues. The high level of miR-494-3p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. Functional study demonstrated that miR-494-3p significantly promoted HCC cell metastasis in vitro and vivo. Since phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a basic oncogenic driver in HCC, a potential role of miR-494-3p was explored as well as its target genes in PI3K/AKT activation. Of all the predicted target genes of miR-494-3p, the tumor-suppressor phosphatase and tensin homolog (PTEN) were identified. In conclusion, the data we collected could define an original mechanism of PI3K/AKT hyperactivation and sketch the regulatory role of miR-494-3p in suppressing the expression of PTEN. Therefore, targeting miR-494-3p could provide an effective therapeutic method for the treatment of the disease.
| S-EPMC6041272 | biostudies-literature
Project description:Recently, it has been reported that miR-324-3p participates in regulation of the carcinogenesis and tumor progression in various cancers. However, the expression and function of miR-324-3p in hepatocellular carcinoma (HCC) remain unclear. In the current study, miR-324-3p expression was significantly up-regulated in HCC tissues and cell lines. HCC patients with high miR-324-3p level showed poor prognostic features and shorter overall survival and disease-free survival. And in vitro and in vivo experiments revealed that miR-324-3p promoted cell viability, colony formation, proliferation and cell cycle progression of HCC cells. Further studies demonstrated that miR-324-3p could directly target DACT1 (dishevelled binding antagonist of beta catenin 1) and negatively regulated its expression in HCC cells. And rescue experiments revealed that DACT1 could reverse the effects of miR-324-3p on HCC cells. Furthermore, the accumulation of both cytoplasmic and nuclear ?-catenin as well as its downstream targets including c-Myc and cyclin D1 could be positively regulated by miR-324-3p. The regulatory effects of miR-324-3p on ?-catenin, c-Myc and cyclin D1 levels could be reversed by DACT1. Overall, we concluded that miR-324-3p could promote tumor growth through targeting DACT1 and activation of Wnt/?-catenin pathway in HCC. MiR-324-3p may be a ponderable and promising therapeutic target for HCC.
| S-EPMC5630364 | biostudies-other
Project description:Circular RNAs (circRNAs) could sponge micro-RNAs (miRNAs) to regulate tumor progression of hepatocellular carcinoma (HCC). Hsa_circ_104566 contributes to papillary thyroid carcinoma progression. However, the tumorigenic mechanism of hsa_circ_104566 on HCC remains enigmatic. The role of hsa_circ_104566 on HCC was therefore evaluated in this study. First, the high expression of hsa_circ_104566 was found in HCC tissues, which was significantly associated with poor prognosis in HCC patients. Second, Hsa_circ_104566 promoted HCC progression by decreasing apoptosis and E-cadherin, while increasing cell viability, proliferation, migration, invasion, and N-cadherin. On the other hand, HCC progression was suppressed by knockdown of hsa_circ_104566. Hsa_circ_104566 could target miR-338-3p, and its expression was negatively correlated with miR-338-3p in HCC patients. Moreover, miR-338-3p suppressed protein expression of Forkhead box protein 1 (FOXP1) and had a negative correlation with FOXP1 in HCC patients. Functional assay further indicated that the promotion of HCC progression by hsa_circ_104566 was reversed by miR-338-3p, and miR-338-3p inhibitor could counteract the effect of hsa_circ_104566 knockdown on the suppression of HCC progression. In vivo assay indicated that hsa_circ_104566 knockdown suppressed HCC tumor growth and metastasis. In conclusion, hsa_circ_104566 sponged miR-338-3p to promote HCC progression, providing a potential therapeutic target for cancer intervention.
| S-EPMC7784580 | biostudies-literature
Project description:ObjectivesEmerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC.Materials and methodsqRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration.ResultsHigh expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p.ConclusionsSTAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.
| S-EPMC6495520 | biostudies-literature