Research Paper|Volume 14, Issue 16|pp 6520—6536

Dicer-mediated miR-200b expression contributes to cell migratory/invasive abilities and cancer stem cells properties of breast cancer cells

Tung-Wei Hsu^1,², Hsin-An Chen,^2,^3,^4,⁵, Po-Hsiang Liao², Yen-Hao Su^2,^3,^4,⁵, Ching-Feng Chiu^5,^6,⁷, Chih-Yang Huang^8,^9,^10,¹¹, Yu-Jung Lin⁸, Chih-Chiang Hung^12,¹³, Ming-Hsin Yeh^14,¹⁵, Shian-Ying Sung^5,^16,^17,^18,^19,²⁰, Chih-Ming Su^2,^3,^4,⁵

¹Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
²Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
³Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
⁴Department of General Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
⁵TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
⁶Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
⁷Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
⁸Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan
⁹Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 97002, Taiwan
¹⁰Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
¹¹Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
¹²Division of Breast Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan
¹³Department of Applied Cosmetology, College of Human Science and Social Innovation, Hungkuang University, Taichung 433, Taiwan
¹⁴Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
¹⁵Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
¹⁶International Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
¹⁷Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan
¹⁸TMU-Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan
¹⁹Clinical Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
²⁰Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan

* Equal contribution

Received: March 25, 2022Accepted: July 12, 2022Published: August 8, 2022

https://doi.org/10.18632/aging.204205

Copyright: © 2022 Hsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Distant metastasis is the leading cause of death in patients with breast cancer. Despite considerable treatment advances, the clinical outcomes of patients with metastatic breast cancer remain poor. CSCs can self-renew, enhancing cancer progression and metastasis. Dicer, a microRNA (miRNA) processing–related enzyme, is required for miRNA maturation. Imbalanced Dicer expression may be pivotal in cancer progression. However, whether and how Dicer affects the stemness of metastatic breast cancer cells remains unclear. Here, we hypothesized that Dicer regulates the migration, invasion, and stemness of breast cancer cells. We established highly invasive cell lines (MCF-7/I-3 and MDA-MB-231/I-3) and observed that Dicer expression was conspicuously lower in the highly invasive cells than in the parental cells. The silencing of Dicer significantly enhanced the cell migratory/invasive abilities and CSCs properties of the breast cancer cells. Conversely, the overexpression of Dicer in the highly invasive cells reduced their migration, invasion, and CSCs properties. Our bioinformatics analyses demonstrated that low Dicer levels were correlated with increased breast cancer risk. Suppression of Dicer inhibited miR-200b expression, whereas miR-200b suppression recovered Dicer knockdown–induced migration, invasion, and cancer stem cells (CSCs) properties of the breast cancer cells. Thus, our findings reveal that Dicer is a crucial regulator of the migration, invasion, and CSCs properties of breast cancer cells and is significantly associated with poor survival in patients with breast cancer.