Background: Circular RNAs (circRNAs) play vital roles in hepatocellular carcinoma development. However, the role and mechanism of circRNA hsa_circ_0000517 (circ_0000517) in hepatocellular carcinoma development were largely unknown. Methods: 45 paired tumor and adjacent nontumor samples were collected from hepatocellular carcinoma patients. The levels of circ_0000517, miR-326 and insulin-like growth factor type 1 receptor (IGF1R) were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, colony ability, migration, invasion and glycolysis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, western blot, transwell assay, glucose consumption, lactate production or adenosine triphosphate (ATP) production. The target correlation between miR-326 and circ_0000517 or IGF1R was analyzed via dual-luciferase reporter analysis. The function of circ_0000517 in vivo was assessed via xenograft model. Results: circ_0000517 expression was elevated in hepatocellular carcinoma tissues and cell lines. circ_0000517 knockdown suppressed cell viability, colony formation, migration, invasion and glycolysis. miR-326 was sponged via circ_0000517 and miR-326 knockdown reversed the effect of circ_0000517 silence on hepatocellular carcinoma development. miR-326 overexpression inhibited hepatocellular carcinoma development through targeting IGF1R. circ_0000517 knockdown decreased IGF1R expression by modulating miR-326. circ_0000517 downregulation reduced xenograft tumor growth. Conclusion: circ_0000517 knockdown repressed hepatocellular carcinoma development in vitro and in vivo by modulating miR-326 and IGF1R.
Background Hepatocellular carcinoma (HCC) is the most common malignant heterogeneous disease in primary liver tumors. Circular RNA hsa_circ_0000517 (hsa_circ_0000517) is connected with HCC prognosis. Nevertheless, there are few studies on the role and mechanism of hsa_circ_0000517 in HCC. Methods Expression of hsa_circ_0000517, miR-326, and SMAD family member 6 (SMAD6) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, colony formation, cell cycle, migration, and invasion were determined though Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound healing, or transwell assays. Protein levels of Cyclin D1, matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), SMAD6, and proliferating cell nuclear antigen (PCNA) were examined with western blot analysis. The relationship between hsa_circ_0000517 or SMAD6 and miR-326 was determined via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The role of hsa_circ_0000517 in vivo was confirmed via xenograft assay. Results Hsa_circ_0000517 and SMAD6 were up-regulated while miR-326 was down-regulated in HCC tissues and cells. Hsa_circ_0000517 down-regulation repressed cell proliferation, colony formation, migration, and invasion, and induced cell cycle arrest in HCC cells in vitro, and constrained tumor growth in vivo. Notably, hsa_circ_0000517 regulated SMAD6 expression via acting as a competing endogenous RNA (ceRNA) for miR-326. And the repressive influence on malignant behaviors of HCC cells mediated by hsa_circ_0000517 inhibition was reversed by miR-326 inhibitors. Moreover, SMAD6 elevation overturned the inhibitory impacts of miR-326 mimics on malignant behaviors of HCC cells. Conclusions Hsa_circ_0000517 depletion repressed HCC advancement via regulating the miR-326/SMAD6 axis.
The long noncoding RNA T cell receptor gamma locus antisense RNA 1 (TRG-AS1) plays an important role in glioblastoma progression. The objective of this study was to determine the expression status of TRG-AS1 in tongue squamous cell carcinoma (TSCC). The regulatory effects of TRG-AS1 depletion on the malignant processes of TSCC cells were illustrated both in vitro and in vivo. Additionally, the precise molecular mechanisms through which TRG-AS promotes TSCC oncogenicity were investigated. TRG-AS1 expression in TSCC tissues and cell lines was detected using reverse transcription-quantitative PCR. Functional experiments including Cell Counting Kit-8 assay, flow cytometric apoptotic assay, migration and invasion assays, and xenograft tumor model analysis were conducted to severally determine the effects of TRG-AS1 on TSCC cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. Herein, TRG-AS1 was highly expressed in TSCC and closely associated with advanced TNM stage, high lymph node metastasis, and poor overall survival. Functionally, TRG-AS1 depletion suppressed TSCC cell proliferation, migration, and invasion in vitro; promoted cell apoptosis; and attenuated tumor growth in vivo. Mechanistically, TRG-AS1 served as a molecular sponge for microRNA-543 (miR-543), thereby contributing to the increased expression of Yes-associated protein 1 (YAP1) -a miR-543 target. Rescue experiments confirmed that miR-543 inhibition or YAP1 overexpression abrogated the anticancer effects of TRG-AS1 silencing in TSCC cells. In conclusion, TRG-AS1 aggravates TSCC malignancy by regulating the miR-543/YAP1 axis. Identification of the TRG-AS1/miR-543/YAP1 regulatory pathway may provide novel insights into TSCC diagnosis, prognosis, and therapy.
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