Bin Xu1, Xiping Zhang2, Shanshan Wang3, Bailing Shi4. 1. Department of Surgery, Zhejiang Rehabilitation Medical Center, Hangzhou 310053, China. Electronic address: xubin789654@sina.com. 2. Department of Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China. 3. Department of Surgery, Zhejiang Rehabilitation Medical Center, Hangzhou 310053, China. 4. Department of Surgery, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China.
Abstract
BACKGROUND: Breast cancer is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying breast cancer metastasis are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer metastasis. In this study, we aimed to analyze the expression and function of miR-449a in breast cancer. MATERIAL AND METHODS: A total of 15 human primary breast cancer tissues and adjacent non-cancerous tissues (10 pairs) were obtained. MiR-449a was examined in tumor tissues and adjacent nontumorous tissues of breast cancer patients and cell lines by real-time PCR. The protein expression levels were analyzed by western blot and immunohistochemistry staining. Luciferase reporter assays was used to validate the target of miR-449a. The effect of miR-449a on breast cancer cell migration and invasion were studied in vitro and in vivo. RESULTS: The expression levels of miR-449a were significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-449a suppressed breast cancer cell proliferation, clone formation, migration, invasion and metastasis in vitro and in vivo. Pleomorphic adenoma gene like-2 (PLAGL2) was identified as a major target of miR-449a. Both overexpression of miR-449a inhibited the expression of PLAGL2 significantly and the knockdown of PLAGL2 expression inhibited the breast cancer cell proliferation and metastasis. CONCLUSION: We demonstrate the miR-449a tumor suppressor role in breast cancer cell migration and invasion via targeting PLAGL2. These findings suggesting that miR-449a/PLAGL2 could serve as a therapeutic strategy for targeting breast cancer.
BACKGROUND:Breast cancer is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying breast cancer metastasis are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer metastasis. In this study, we aimed to analyze the expression and function of miR-449a in breast cancer. MATERIAL AND METHODS: A total of 15 human primary breast cancer tissues and adjacent non-cancerous tissues (10 pairs) were obtained. MiR-449a was examined in tumor tissues and adjacent nontumorous tissues of breast cancerpatients and cell lines by real-time PCR. The protein expression levels were analyzed by western blot and immunohistochemistry staining. Luciferase reporter assays was used to validate the target of miR-449a. The effect of miR-449a on breast cancer cell migration and invasion were studied in vitro and in vivo. RESULTS: The expression levels of miR-449a were significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-449a suppressed breast cancer cell proliferation, clone formation, migration, invasion and metastasis in vitro and in vivo. Pleomorphic adenoma gene like-2 (PLAGL2) was identified as a major target of miR-449a. Both overexpression of miR-449a inhibited the expression of PLAGL2 significantly and the knockdown of PLAGL2 expression inhibited the breast cancer cell proliferation and metastasis. CONCLUSION: We demonstrate the miR-449atumor suppressor role in breast cancer cell migration and invasion via targeting PLAGL2. These findings suggesting that miR-449a/PLAGL2 could serve as a therapeutic strategy for targeting breast cancer.
Authors: Zhenze Zhao; Spencer D Shelton; Alejandro Oviedo; Amy L Baker; Collin P Bryant; Soroush Omidvarnia; Liqin Du Journal: J Exp Clin Cancer Res Date: 2020-02-22
Authors: Lai-Sheung Chan; Hong-Lok Lung; Roger Kai-Cheong Ngan; Anne Wing-Mui Lee; Sai Wah Tsao; Kwok-Wai Lo; Michael Kahn; Maria Li Lung; Rotraud Wieser; Nai-Ki Mak Journal: Int J Mol Sci Date: 2020-07-31 Impact factor: 5.923