Open Access

miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma

  • Authors:
    • Jinjian Gao
    • Sai Ma
    • Fan Yang
    • Xu Chen
    • Wei Wang
    • Jianping Zhang
    • Yufang Li
    • Tao Wang
    • Lequn Shan
  • View Affiliations

  • Published online on: April 29, 2020     https://doi.org/10.3892/or.2020.7601
  • Pages: 139-155
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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July 2020
Volume 44 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Gao, J., Ma, S., Yang, F., Chen, X., Wang, W., Zhang, J. ... Shan, L. (2020). miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma. Oncology Reports, 44, 139-155. https://doi.org/10.3892/or.2020.7601
MLA
Gao, J., Ma, S., Yang, F., Chen, X., Wang, W., Zhang, J., Li, Y., Wang, T., Shan, L."miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma". Oncology Reports 44.1 (2020): 139-155.
Chicago
Gao, J., Ma, S., Yang, F., Chen, X., Wang, W., Zhang, J., Li, Y., Wang, T., Shan, L."miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma". Oncology Reports 44, no. 1 (2020): 139-155. https://doi.org/10.3892/or.2020.7601