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Association of RDM1 with osteosarcoma progression via cell cycle and MEK/ERK signalling pathway regulation |
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| Authors: | Jun Sheng Kun Liu Dawei Sun Piming Nie Zhiping Mu Hui Chen Zhengfeng Zhang |
| Affiliation: | 1. Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing, China Contribution: Conceptualization (equal), Investigation (equal);2. Department of Orthopedic Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, China Contribution: Investigation (equal);3. Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing, China Contribution: Investigation (equal);4. College of Life Sciences, Zhejiang University, Hangzhou, China;5. Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing, China |
| Abstract: | RAD52 motif-containing 1 (RDM1), a key regulator of DNA double-strand break repair and recombination, has been reported to play an important role in the development of various human cancers, such as papillary thyroid carcinoma, neuroblastoma and lung cancer. However, the effect of RDM1 on osteosarcoma (OS) progression remains unclear. Here, this study mainly explored the connection between RDM1 and OS progression, as well as the underlying mechanism. It was found that RDM1 was highly expressed in OS cells compared with human osteoblast cells. Knockdown of RDM1 caused OS cell proliferation inhibition, cell apoptosis promotion and cell cycle arrest at G1 stage, whereas RDM1 overexpression resulted in the opposite phenotypes. Furthermore, RDM1 silencing leads to a significant decrease in tumour growth in xenograft mouse model. RDM1 also increased the protein levels of MEK 1/2 and ERK 1/2. All these findings suggest that RDM1 plays an oncogenic role in OS via stimulating cell cycle transition from G1 to S stage, and regulating MEK/ERK signalling pathway, providing a promising therapeutic factor for the treatment of OS. |
| Keywords: | cell cycle MEK/ERK signalling pathway Osteosarcoma RDM1 |