MicroRNA‑22 regulates autophagy and apoptosis in cisplatin resistance of osteosarcoma

Meng,Chen‑Yang; Zhao,Zhen‑Qun; Bai,Rui; Zhao,Wei; Wang,Yu‑Xing; Sun,Liang; Sun,Chao; Feng,Wei; Guo,Shi‑Bing

doi:10.3892/mmr.2020.11447

MicroRNA‑22 regulates autophagy and apoptosis in cisplatin resistance of osteosarcoma

Authors:
- Chen‑Yang Meng
- Zhen‑Qun Zhao
- Rui Bai
- Wei Zhao
- Yu‑Xing Wang
- Liang Sun
- Chao Sun
- Wei Feng
- Shi‑Bing Guo
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Affiliations: Department of Orthopedic Surgery, Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010030, P.R. China
Published online on: August 20, 2020 https://doi.org/10.3892/mmr.2020.11447
Pages: 3911-3921
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma (OS) is a primary malignant tumor of bone tissue. Effective chemotherapy may improve the survival of patients with OS. MicroRNAs (miRs) serve significant roles in the regulatory function of tumorigenesis and chemosensitivity of different types of cancer. miR‑22 has been revealed to inhibit the proliferation and migration of OS cells, as well as increasing their sensitivity to cisplatin (CDDP). The mechanisms of action behind the functions of miR‑22 in OS drug resistance require investigation. Therefore, in the present study, the human OS cell lines (MG‑63, U2OS, Saos2 and OS9901) and a drug‑resistant cell line (MG‑63/CDDP) were cultured. Cell proliferation, apoptosis and autophagy assays were performed to investigate the proliferation, apoptosis and autophagy of cell lines transfected with miR‑22 mimic. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to investigate the expression levels of associated genes. The results revealed that miR‑22 inhibited the proliferation of MG‑63 cells and MG‑63/CDDP cells, and enhanced the anti‑proliferative ability of CDDP. miR‑22 induced apoptosis and inhibited autophagy of MG‑63 cells and MG‑63/CDDP cells. Apoptosis‑related genes, including caspase‑3 and Bcl‑2‑associated X protein were upregulated, while B‑cell lymphoma‑2 was downregulated in both cell lines transfected with the miR‑22 mimic. Autophagy protein 5, beclin1 and microtubules‑associated protein 1 light chain 3 were downregulated in both cell lines transfected with miR‑22 mimic. Furthermore, the in vitro and in vivo expression levels of metadherin (MTDH) in the OS/OS‑CDDP‑resistant models were downregulated following transfection with the miR‑22 mimic. Therefore, the results of the present study suggested that miR‑22 promoted CDDP sensitivity by inhibiting autophagy and inducing apoptosis in OS cells, while MTDH may serve a positive role in inducing CDDP resistance of OS cells.

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