High intensity focused ultrasound inhibits melanoma cell migration and metastasis through attenuating microRNA-21-mediated PTEN suppression

// Huan Li 1, * , Shi-mei Yuan 1, * , Min Yang 1 , He Zha 1 , Xue-ru Li 1 , Hui Sun 1 , Liang Duan 1 , Yue Gu 1 , Ai-fang Li 1 , Ya-guang Weng 1 , Jin-yong Luo 1 , Tong-chuan He 1, 3 , Yan Wang 2 , Chong-yan Li 2 , Fa-qi Li 2 , Zhi-biao Wang 2 , Lan Zhou 1 1 Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China 2 State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China 3 Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA * These authors have contributed equally to this work Correspondence to: Lan Zhou, email: zhoulan0111@foxmail.com Keywords: High intensity focused ultrasound (HIFU), melanoma, metastasis, microRNA-21, PTEN Received: December 23, 2015 Accepted: May 28, 2016 Published: July 6, 2016 ABSTRACT High intensity focused ultrasound (HIFU) technology is becoming a potential noninvasive treatment for solid tumor. To explore whether HIFU can be applied to treat melanoma and its metastasis, we investigated the effect of HIFU on murine melanoma model. While there was little influence on cell survival, viability or apoptosis, HIFU exposure suppressed melanoma cell migration in vitro and metastasis in vivo . The expression of microRNA-21(miR-21) was down-regulated and PTEN expression was up-regulated in response to HIFU exposure, which was in concomitant with the reduction of AKT activity. Furthermore, ectopic miR-21 expression suppressed this effect of HIFU. These results demonstrate that HIFU exposure can inhibit AKT-mediated melanoma metastasis via miR-21 inhibition to restore PTEN expression. Therefore, targeting the miR-21/PTEN/AKT pathway might be a novel strategy of HIFU in treatment of melanoma.