OncoTargets and Therapy (Dec 2019)
miR-520b Promotes Breast Cancer Stemness Through Hippo/YAP Signaling Pathway
Abstract
Hui Zhang,1–4,* Ting-yuan Lang,5,* Dong-ling Zou,5 Lei Zhou,6–8 Meng Lou,5 Jing-shu Liu,9 Yun-zhe Li,9 Dong-yan Ding,9 Yu-cong Li,5,9 Na Zhang,5 Xiao-dong Zheng,2 Xiao-hua Zeng,2 Qi Zhou,1,3–5 Li Li1 1Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 2Breast Cancer Center, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of China; 4Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, Chongqing, 400030, People’s Republic of China; 5Department of Gynecologic Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of China; 6Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; 7Singapore Eye Research Institute, Singapore 169856, Singapore; 8Ophthalmology and Visual Sciences Academic Clinical Research Program, Duke-NUS Medical School, Singapore 169867, Singapore; 9Bioengineering College of Chongqing University, Chongqing University, Chongqing 400030, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li LiDepartment of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of ChinaEmail [email protected] ZhouDepartment of Gynecologic Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of ChinaEmail [email protected]: The breast cancer stem cells contribute to the initiation, progression, recurrence, metastasis as well as resistance of breast cancer. However, the mechanisms underlying the maintenance of breast cancer stemness have not been fully understood.Materials and methods: TCGA and GEO data were used for measuring miR-520b expression in breast cancer tissues. Kaplan-meier analysis was used for determining the relationship between miR-520b expression level and the prognosis of patients. Genetic manipulation was performed by lentivirus system and miR-520b inhibitor was used for knockdown of miR-520b. qRT-PCR and Western blot were employed to determine the mRNA and protein levels, respectively. The stemness and EMT (Epithelial to mesenchymal transition) were assessed by sphere-formation and transwell assay as well as the expression of the related markers. The target genes of miR-520b were identified using the online database starBase V3.0.Results: miR-520b is upregulated in cancer tissues of breast cancer patients and predicts poor prognosis. Upregulation of miR-520b was found in breast cancer stem cells. Ectopic expression of miR-520b promotes the stemness of the breast cancer cells, conversely, depletion of miR-520b attenuates the stemness of these cells. miR-520b positively regulates Hippo/YAP signaling pathway and overexpression of LAST2 abolished the effect of miR-520b on the stemness of breast cancer cells.Conclusion: miR-520b promotes the stemness of breast cancer patients by activating Hippo/YAP signaling via targeting LATS2.Keywords: miR-520b, breast cancer, stemness, Hippo/YAP, LATS2
