Cyclin L1 participates in Adriamycin resistance and progression of osteosarcoma via PI3K/AKT-mTOR pathway

细胞周期蛋白L1通过PI3K/AKT-mTOR通路参与骨肉瘤阿霉素耐药及进展

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作者:Yanbin Zhang, Tao Zhang, Long Chen, Zijun Guo, Xiaobing Jiang

Abstract

Chemoresistance is a common and thorny problem in the treatment of osteosarcoma (OS), which obstructs the response of relapse or metastasis of OS to chemotherapy and leads to the unfavorable prognosis of OS patients. Cyclin L1 (CCNL1) is a non-canonical cyclin that plays an important role in the regulation of tumor cell proliferation and lymph node metastasis. In this work, we explored the impact of CCNL1 expression levels on proliferation, migration, and Adriamycin (ADM) resistance in OS and related mechanisms. We found that CCNL1 expression levels were significantly associated with clinical prognosis of patients with OS and CCNL1 could promote OS proliferation and migration. In addition, we also revealed that cellular CCNL1 was significantly increased in ADM-resistant OS cells and promoted ADM resistance. The PI3K/AKT-mTOR pathway is involved in CCNL1-mediated ADM resistance in OS. In summary, CCNL1 is involved in the progression of ADM resistance and OS through the PI3K/AKT-mTOR pathway, which will provide a new clue to the mechanism of ADM resistance and a potential target for the treatment of ADM-resistant OS.

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