CircORC2 promoted proliferation and inhibited the sensitivity of osteosarcoma cell lines to cisplatin by regulating the miR-485-3p/TRIM2 axis

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Tianhua Chen, Zuyang Zhang, Chao Tian, Yuchao Feng, Xiaojie He, Liangdong Jiang
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Abstract

Resistance to chemotherapy leads to poor prognosis for osteosarcoma (OS) patients. However, due to the high metastasis of tumor and the decrease in sensitivity of tumor cells to cisplatin (DDP), the 5-year survival rate of OS patients is still unsatisfactory. This study explored a mechanism for improving the sensitivity of OS cells to DDP. A DDP-resistant OS cell model was established, and we have found that circORC2 and TRIM2 were upregulated in DDP-resistant OS cells, but miR-485-3p was downregulated. The cell viability and proliferation of the OS cells decreased gradually with the increase of DDP dose, but a gradual increase in apoptosis was noted. CircORC2 promoted OS cell proliferation and DDP resistance and upregulated TRIM2 expression by targeting miR-485-3p. Functionally, circORC2 downregulated miR-485-3p to promote OS cell proliferation and inhibit DDP sensitivity. Additionally, it promoted cell proliferation and inhibited the sensitivity of DDP by regulating the miR-485-3p/TRIM2 axis. In conclusion, circORC2 promoted cell proliferation and inhibited the DDP sensitivity in OS cells via the miR-485-3p/TRIM2 axis. These findings indicated the role of circORC2 in regulating the sensitivity of OS cells to DDP.

Abstract Image

CircORC2 通过调控 miR-485-3p/TRIM2 轴促进骨肉瘤细胞株的增殖并抑制其对顺铂的敏感性。
化疗抗药性导致骨肉瘤(OS)患者预后不良。然而,由于肿瘤的高度转移性和肿瘤细胞对顺铂 (DDP) 敏感性的降低,骨肉瘤患者的 5 年生存率仍然不尽如人意。本研究探索了提高 OS 细胞对 DDP 敏感性的机制。我们发现,在对DDP耐药的OS细胞中,circORC2和TRIM2上调,但miR-485-3p下调。随着DDP剂量的增加,OS细胞的存活率和增殖率逐渐下降,但凋亡率逐渐增加。CircORC2通过靶向miR-485-3p促进了OS细胞的增殖和DDP抗性,并上调了TRIM2的表达。从功能上讲,circORC2下调miR-485-3p,促进OS细胞增殖并抑制DDP敏感性。此外,它还通过调控miR-485-3p/TRIM2轴促进细胞增殖并抑制对DDP的敏感性。总之,circORC2通过miR-485-3p/TRIM2轴促进OS细胞增殖并抑制DDP敏感性。这些发现表明circORC2在调节OS细胞对DDP的敏感性方面发挥了作用。
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来源期刊
CiteScore
6.40
自引率
4.90%
发文量
40
期刊介绍: The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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