miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma
| Autor: | Yufang Li, Lequn Shan, Jinjian Gao, Tao Wang, Sai Ma, Xu Chen, Jianping Zhang, Wei Wang, Fan Yang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Bone Neoplasms Biology medicine.disease_cause Metastasis Proto-Oncogene Proteins c-myc Proto-Oncogene Proteins p21(ras) Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement oncogene Cell Line Tumor microRNA medicine Animals Humans Neoplasm Metastasis 3' Untranslated Regions Osteosarcoma Oncogene Articles General Medicine Cell cycle medicine.disease Gene Expression Regulation Neoplastic MicroRNAs cell proliferation 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Stathmin Female KRAS Carcinogenesis carcinogenesis Neoplasm Transplantation |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2020.7601 |
| Popis: | Emerging evidence has indicated that microRNAs (miRs) are involved in the malignant behavior of cancer. The present study explored the role of miR-193b in the development and metastasis of osteosarcoma. Compared with F4 osteosarcoma cells, which have a relatively low metastatic potential, highly metastatic F5M2 cells exhibited a lower expression of miR-193b. Furthermore, miR-193b exerted negative effects on cell proliferation, colony formation, cell cycle progression, migration and invasion, and induced apoptosis. In vivo studies revealed negative influences of miR-193b on tumorigenesis and metastasis. The tumor-suppressive role of miR-193b was achieved by targeting KRAS and stathmin 1 (STMN1). Notably, overexpression of KRAS and STMN1 attenuated the miR-193b-induced inhibition of malignant behaviors. There was a double-negative regulatory loop between MYC and miR-193b, with MYC inhibiting miR-193b expression by directly binding to its promoter region and miR-193b negatively influencing MYC expression indirectly through some unknown mechanism. Collectively, these findings indicated that miR-193b may serve a tumor suppressive role in osteosarcoma by targeting KRAS and STMN1. The double-negative regulatory loop between MYC and miR-193b may contribute to the sustained upregulation of MYC, the downregulation of miR-193b, and to the subsequently enhanced expression of KRAS and STMN1, which may eventually lead to the development and metastasis of osteosarcoma. |
| Databáze: | OpenAIRE |
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