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As a subclass of noncoding RNAs, circular RNA play an important role in tumour development. The aim of this study was to investigate the role of circ_0004674 in osteosarcoma glycolysis and the molecular mechanism of its regulation. We examined the expression of circ_0004674, miR-140-3p, TCF4 and glycolysis-related proteins (including HK2, PKM2, GLUT1 and LDHA) in osteosarcoma cells and tissues by quantitative reverse transcription-polymerase chain reaction and immunoblotting (Western blot analysis). The role of circ_0004674, miR-140-3p and TCF4 in the proliferation, apoptosis, migration and invasion of OS cells was examined using CCK8 assay, Apoptosis assay, Wound healing assay, Transwell migration and Matrigel invasion assay. The interaction of circ_0004674/miR-140-3p and miR-1543/TCF4 was also analysed using a dual luciferase reporter assay. Finally, the glycolytic process was assessed by glucose uptake assays and lactate production measurements. The results showed that the expression of circ_0004674 and TCF4 was significantly higher in MG63 and U2OS cells compared to hFOB1.19 cells, while the expression of miR-140-3p was downregulated. Silencing of circ_0004674 gene significantly inhibited the proliferation, migration and invasion of cancer cells and promoted apoptosis of cancer cells. Experiments such as dual luciferase reporter analysis showed that circ_0004674 regulates the expression of glycolysis-related proteins through the miR-140-3p/TCF4 pathway, and inhibition of this gene attenuated the depletion of glucose content and the production of lactate in cancer cells. Furthermore, inhibition of miR-140-3p or overexpression of TCF could reverse the phenotypic changes in cancer cells induced by circ_0004674 silencing. In summary, this study elucidated the specific function and potential mechanisms of circ_0004674 in osteosarcoma glycolysis. The findings demonstrate that miR-140-3p and TCF4 function respectively as a tumor suppressor gene and an oncogene in osteosarcoma. Notably, they influence glycolysis and associated pathways, regulating osteosarcoma proliferation. Therefore, circ_0004674 promotes osteosarcoma glycolysis and proliferation through the miR-140-3p/TCF4 pathway, enhancing the malignant behaviour of tumours, and it is expected to be a potential molecular target for osteosarcoma treatment.
Asunto(s)
Proliferación Celular , Glucólisis , MicroARNs , Osteosarcoma , ARN Circular , Factor de Transcripción 4 , Humanos , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , ARN Circular/genética , ARN Circular/metabolismo , Factor de Transcripción 4/metabolismo , Factor de Transcripción 4/genética , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Transducción de SeñalRESUMEN
@#Osteosarcoma(OS)is one of the most common malignant tumors in bone tissue,and its specific mechanism is not yet fully clear. Studies have shown that OS cells express different cytokines(CKs)and their receptors in the development stage of tumors,and enable them to grow autonomously and confer metastatic ability through autocrine and paracrine effects. In this regard,the most important CKs mainly includes insulin-like growth factor-1,transforming growth factor-β,chemokine 5 and interleukin-8,which can regulate the tumor microenvironment that is conducive to tumor growth,invasion and metastasis. This review summarizes the role and mode of action of CKs and their biological relevance to OS cells,hoping to provide effective new markers and therapeutic targets for clinical treatment of OS.
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The incidence of osteosarcoma (OS) is increasing year by year, and the prognosis of patients with advanced OS is extremely poor due to the tendency of recurrence and chemotherapy resistance after surgery. Ferroptosis is a novel form of programmed cell death (PCD) that kills cells through iron-dependent lipid peroxidation. Current studies have shown that ferroptosis is closely related to OS and could reduce chemotherapy resistance to a certain extent, which has great therapeutic potential. In this paper, we review the regulatory mechanism of ferroptosis and its research progress in OS, hoping to provide new help for the clinical treatment of OS.
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Introduction Bushen Zhuangjin Decoction (BZD), a well-known formulation in Traditional Chinese Medicine, has been widely used for the treatment of osteoarthritis (OA). Due to the poor intrinsic repair capacity of chondrocytes, promoting the proliferation of chondrocytes is an efficient treatment to delay the progression of cartilage degradation.Hypothesis/Gap Statement Therefore, to explore the regulatory mechanism of Bushen Zhuangjin Decoction in chondrocytes will contribute to the repair of chondrocyte injury in OA, and may serve as a potential therapy for OA diseases.Aim To investigate the expression and distribution of SOX9 mediated by serum containing Bushen Zhuangjin Decoction (BZD) and its therapeutic effect on chondrocyte injury in rats.Methodology. The subcultured second-generation rat chondrocytes were randomly divided into four groups, and they were intervened with medium containing different serums, including: blank serum group, low-concentration BZD group, medium-concentration BZD group, and high-concentration BZD group. The viability, proliferation and apoptosis of chondrocytes were detected by MTT assay and flow cytometry. The gene and protein levels of SOX9, aggrecan and type II collagen genes were analysed by qRT-PCR and Western blot analysis. Immunofluorescence staining was used to analyse the expression and distribution of SOX9. Inflammatory factors in different culture mediums of chondrocytes were detected by ELISA.Results Compared with the control group, the activity of chondrocytes in the BZD drug-containing serum group was significantly enhanced, and the degree of apoptosis was significantly decreased. The gene and protein levels of SOX9, proteoglycan aggrecan and collagen II in chondrocytes increased significantly. The inflammatory factors in the culture medium also decreased significantly. And in the above experiments, the medium concentration group BZD drug-containing serum had the best effect.Conclusion Our research results show that BZD medicated serum can up-regulate the expression of SOX9, reduce the release of inflammatory factors, and promote changes in the phenotype of chondrocytes, which protects chondrocytes from damage.