Molecular Therapy: Oncolytics (Mar 2022)
Exosomal miR-205-5p enhances angiogenesis and nasopharyngeal carcinoma metastasis by targeting desmocollin-2
- Wenjuan Yang,
- Shiming Tan,
- Lixia Yang,
- Xiaohui Chen,
- Ruiqian Yang,
- Linda Oyang,
- Jinguan Lin,
- Longzheng Xia,
- Nayiyuan Wu,
- Yaqian Han,
- Yanyan Tang,
- Min Su,
- Xia Luo,
- Yiqing Yang,
- Lisheng Huang,
- Zifan Hu,
- Yi Tao,
- Lin Liu,
- Yi Jin,
- Hui Wang,
- Qianjin Liao,
- Yujuan Zhou
Affiliations
- Wenjuan Yang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Shiming Tan
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Lixia Yang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Xiaohui Chen
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China; University of South China, West Changsheng Road, Hengyang 421001, Hunan, China
- Ruiqian Yang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China; University of South China, West Changsheng Road, Hengyang 421001, Hunan, China
- Linda Oyang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Jinguan Lin
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Longzheng Xia
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Nayiyuan Wu
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Yaqian Han
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Yanyan Tang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Min Su
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Xia Luo
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Yiqing Yang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Lisheng Huang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Zifan Hu
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Yi Tao
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Lin Liu
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Yi Jin
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China
- Hui Wang
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China; Hunan Key Laboratory of Translational Radiation Oncology, 283 Tongzipo Road, Changsha 410013, Hunan, China; Corresponding author Hui Wang, Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China.
- Qianjin Liao
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China; Hunan Key Laboratory of Translational Radiation Oncology, 283 Tongzipo Road, Changsha 410013, Hunan, China; Corresponding author Qianjin Liao, Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China.
- Yujuan Zhou
- Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China; Hunan Key Laboratory of Translational Radiation Oncology, 283 Tongzipo Road, Changsha 410013, Hunan, China; Corresponding author Yujuan Zhou, Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha 410013, Hunan, China.
- Journal volume & issue
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Vol. 24
pp. 612 – 623
Abstract
The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3′ UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.