Qing Tian1, Yufan Gu1, Feifei Wang1, Lijun Zhou2, Zhipeng Dai3, Hongjian Liu1, Xuejian Wu1, Xinxing Wang4, Yong Liu2, Songfeng Chen5, Qicai Han6. 1. Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. 2. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. 3. Department of Orthopaedics, Henan Provincial People's Hospital, Zhengzhou, Henan 450030, China. 4. Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. 5. Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: chensongfeng1234@yandex.com. 6. Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address: hanqicai9778@126.com.
Abstract
BACKGROUND: Osteosarcoma (OS) is a primary malignant bone sarcoma in human worldwide. It has been shown that the level of microRNA-154-5p (miR-154-5p) was downregulated in human OS tissues. However, the mechanisms by which miR-154-5p regulates the proliferation, apoptosis and invasion in OS remain unclear. Thus, the present study aimed to investigate the role of miR-154-5p during the tumorigenesis of OS. METHODS: The level of miR-154-5p in human OS tissues was detected by RT-qPCR. In addition, the effects of miR-154-5p on apoptosis and invasion of OS cells were assessed by flow cytometry and transwell assays, respectively. Meanwhile, the dual luciferase reporter system assay was performed to explore the interaction of miR-154-5p and E2F5. RESULTS: The level of miR-154-5p was downregulated in OS tissues. Overexpression of miR-154-5p significantly inhibited the proliferation, migration and invasion of MG63 cells. In addition, upregulation of miR-154-5p obviously induced apoptosis in MG63 cells via upregulation of Bax and cleaved caspase 3, and downregulation of Bcl-2. Moreover, luciferase reporter assay identified that E2F5 was the binding target of miR-154-5p. Meanwhile, overexpression of miR-154-5p induced cell cycle arrest in MG63 cells via inhibiting the expressions of E2F5, Cyclin E1 and CDK2. Furthermore, in vivo assays indicated that overexpression of miR-154-5p notably inhibited the tumor growth in an OS xenograft model. CONCLUSION: These results indicated that miR-154-5p may function as a potential tumor suppressor in OS. Therefore, miR-154-5p might be a novel therapeutic option for the treatment of OS.
BACKGROUND:Osteosarcoma (OS) is a primary malignant bone sarcoma in human worldwide. It has been shown that the level of microRNA-154-5p (miR-154-5p) was downregulated in human OS tissues. However, the mechanisms by which miR-154-5p regulates the proliferation, apoptosis and invasion in OS remain unclear. Thus, the present study aimed to investigate the role of miR-154-5p during the tumorigenesis of OS. METHODS: The level of miR-154-5p in human OS tissues was detected by RT-qPCR. In addition, the effects of miR-154-5p on apoptosis and invasion of OS cells were assessed by flow cytometry and transwell assays, respectively. Meanwhile, the dual luciferase reporter system assay was performed to explore the interaction of miR-154-5p and E2F5. RESULTS: The level of miR-154-5p was downregulated in OS tissues. Overexpression of miR-154-5p significantly inhibited the proliferation, migration and invasion of MG63 cells. In addition, upregulation of miR-154-5p obviously induced apoptosis in MG63 cells via upregulation of Bax and cleaved caspase 3, and downregulation of Bcl-2. Moreover, luciferase reporter assay identified that E2F5 was the binding target of miR-154-5p. Meanwhile, overexpression of miR-154-5p induced cell cycle arrest in MG63 cells via inhibiting the expressions of E2F5, Cyclin E1 and CDK2. Furthermore, in vivo assays indicated that overexpression of miR-154-5p notably inhibited the tumor growth in an OS xenograft model. CONCLUSION: These results indicated that miR-154-5p may function as a potential tumor suppressor in OS. Therefore, miR-154-5p might be a novel therapeutic option for the treatment of OS.
Authors: Yangjin Bae; Huan-Chang Zeng; Yi-Ting Chen; Shamika Ketkar; Elda Munivez; Zhiyin Yu; Francis H Gannon; Brendan H Lee Journal: JBMR Plus Date: 2022-04-09