Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes

Sun,Liang; He,Miao; Xu,Ning; Xu,Da-Hai; Ben-David,Yaacov; Yang,Zhao-Ying; Li,You-Jun

doi:10.3892/ijo.2018.4571

Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes

Authors:
- Liang Sun
- Miao He
- Ning Xu
- Da-Hai Xu
- Yaacov Ben-David
- Zhao-Ying Yang
- You-Jun Li
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Affiliations: Department of Human Anatomy, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Anesthesia, The Second Hospital of Jilin University, Changchun, Jilin 130022, P.R. China, State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: September 25, 2018 https://doi.org/10.3892/ijo.2018.4571
Pages: 2705-2714

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Abstract

Breast cancer is one of the main types of cancer affecting the health of females worldwide. Despite improvements in therapeutic approaches, cancer patients succumb to the disease due to metastasis itself, rather than the primary tumor from which metastases arise, emphasizing the need for the better understanding of the biological bases that contribute to disease progression. RAB22A, a member of the proto-oncogene RAS family, plays an important role in the formation, trafficking and metabolism of exosomes, and is associated with the occurrence and development of multiple human cancers. In this study, we demonstrate that the upregulation of RAB22A is associated with breast cancer progression and lymph node metastasis. We identified a signature of RAB22A and miR-193b that exhibited a negative association in metastatic as opposed to the surrounding normal cells, and RAB22A was identified as the target gene of miR-193b. While RAB22A was found to regulate exosomes-mediated breast cancer cell proliferation, invasion and migration, these biological characteristics were diminished in the breast cancer cells in which the RAB22A gene was knocked down or in the cells in which the exosomes were dissolved by proteinase K/RNase treatment. On the whole, the findings of this study demonstrate the critical role that miR-193b plays in the regulation of RAB22A-mediated exosome function during cancer growth and metastasis, which may have significant implications on cancer therapy.

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