Heliyon (Jul 2024)
MiR-30c suppresses the proliferation, metastasis and polarity reversal of tumor cell clusters by targeting MTDH in invasive micropapillary carcinoma of the breast
- Yunwei Han,
- Weidong Li,
- Renyong zhi,
- Gui Ma,
- Ang Gao,
- Kailiang Wu,
- Hui Sun,
- Dan Zhao,
- Yiling Yang,
- Fangfang Liu,
- Feng Gu,
- Xiaojing Guo,
- Jintang Dong,
- Shuai Li,
- Li Fu
Affiliations
- Yunwei Han
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Weidong Li
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Renyong zhi
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Gui Ma
- Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China; Southern University of Science and Technology, School of Medicine, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China; Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365C Clifton Road, Atlanta, 30322, Georgia, USA
- Ang Gao
- Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China; Southern University of Science and Technology, School of Medicine, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China; Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365C Clifton Road, Atlanta, 30322, Georgia, USA
- Kailiang Wu
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Hui Sun
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Dan Zhao
- Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China; Southern University of Science and Technology, School of Medicine, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China; Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365C Clifton Road, Atlanta, 30322, Georgia, USA
- Yiling Yang
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Fangfang Liu
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Feng Gu
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Xiaojing Guo
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China
- Jintang Dong
- Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China; Southern University of Science and Technology, School of Medicine, 1088 Xueyuan Road, Shenzhen, Guangdong 518055, China; Emory Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365C Clifton Road, Atlanta, 30322, Georgia, USA
- Shuai Li
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China; Corresponding author. Department of Breast Pathology and Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Ministry of Education, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China.
- Li Fu
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center of Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China; Ministry of Education, Breast Cancer Innovation Team of the Ministry of Education, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Breast Cancer Research, Tianjin 300060, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China; Corresponding author. Department of Breast Pathology and Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Ministry of Education, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin 300060, China.
- Journal volume & issue
-
Vol. 10,
no. 13
p. e33938
Abstract
Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an ‘inside-out’ growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear. Methods: and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3′UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results: We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3′UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the ‘inside-out’ growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients. Conclusions: Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.