MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8
Liangliang Dong,1 Dongmei Zhou,2 Chunxia Xin,3 Bing Liu,3 Ping Sun3 1Department of Medical Oncology, Yantai Yuhuangding Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Oncology, Yantai Shan Hospital, Yantai 2640...
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Dove Medical Press
2020-09-01
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Series: | Cancer Management and Research |
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Online Access: | https://www.dovepress.com/microrna-139-suppresses-the-tumorigenicity-of-triple-negative-breast-c-peer-reviewed-article-CMAR |
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author | Dong L Zhou D Xin C Liu B Sun P |
author_facet | Dong L Zhou D Xin C Liu B Sun P |
author_sort | Dong L |
collection | DOAJ |
description | Liangliang Dong,1 Dongmei Zhou,2 Chunxia Xin,3 Bing Liu,3 Ping Sun3 1Department of Medical Oncology, Yantai Yuhuangding Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Oncology, Yantai Shan Hospital, Yantai 264000, People’s Republic of China; 3Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, People’s Republic of ChinaCorrespondence: Ping SunDepartment of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Zhifu District, Yantai 264000, People’s Republic of ChinaTel +86-13963896536Email sunping20039@hotmail.comPurpose: The effects of miR-139 on the tumorigenicity of triple negative breast cancer (TNBC) and the underlying mechanisms were investigated.Methods: Normal human breast epithelial (MCF-10A) and TNBC cell lines (HCC1806 and BT549) were used for microRNA (miR)-139 overexpression, SOX8 overexpression, and knockdown studies as in vitro models of TNBC. The expression of SOX8 and miR-139 was detected by reverse transcription-polymerase chain reaction. CCK8 and clone formation assays were used to evaluate cell proliferation ability. Transwell assays and flow cytometry were used to test cell migration and apoptosis, respectively. Cell tumorigenicity was examined by tumor sphere formation assays. The interaction between miR-139 and SOX8 was examined by dual-luciferase reporter assays. The expression of SOX8, cleaved caspase-3, and cleaved caspase-9 was analyzed by Western blotting. The findings were validated in vivo using a nude mouse transplanted tumor model.Results: SOX8 expression was higher (P < 0.05) and miR-139 expression was lower (P < 0.05) in HCC1806 and BT549 cells than in MCF-10A cells. SOX8 overexpression significantly enhanced cell proliferation and migration, reduced the rate of cell apoptosis, and increased tumor sphere formation (P < 0.05) compared with the control group, whereas SOX8 knockdown had the opposite effect (P < 0.05). Overexpression of miR-139 markedly decreased cell proliferation and migration, increased cell apoptosis in vitro, and decreased tumor angiogenesis and volume in vivo (P < 0.05).Conclusion: miR-139 suppressed the tumorigenicity of TNBC cells by targeting SOX8.Keywords: breast cancer, carcinogenesis, molecular targets, gene regulation |
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spelling | doaj.art-29d7106287c24b5ab83596288174dbfd2022-12-22T00:20:52ZengDove Medical PressCancer Management and Research1179-13222020-09-01Volume 129417942857587MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8Dong LZhou DXin CLiu BSun PLiangliang Dong,1 Dongmei Zhou,2 Chunxia Xin,3 Bing Liu,3 Ping Sun3 1Department of Medical Oncology, Yantai Yuhuangding Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 2Department of Oncology, Yantai Shan Hospital, Yantai 264000, People’s Republic of China; 3Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, People’s Republic of ChinaCorrespondence: Ping SunDepartment of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Zhifu District, Yantai 264000, People’s Republic of ChinaTel +86-13963896536Email sunping20039@hotmail.comPurpose: The effects of miR-139 on the tumorigenicity of triple negative breast cancer (TNBC) and the underlying mechanisms were investigated.Methods: Normal human breast epithelial (MCF-10A) and TNBC cell lines (HCC1806 and BT549) were used for microRNA (miR)-139 overexpression, SOX8 overexpression, and knockdown studies as in vitro models of TNBC. The expression of SOX8 and miR-139 was detected by reverse transcription-polymerase chain reaction. CCK8 and clone formation assays were used to evaluate cell proliferation ability. Transwell assays and flow cytometry were used to test cell migration and apoptosis, respectively. Cell tumorigenicity was examined by tumor sphere formation assays. The interaction between miR-139 and SOX8 was examined by dual-luciferase reporter assays. The expression of SOX8, cleaved caspase-3, and cleaved caspase-9 was analyzed by Western blotting. The findings were validated in vivo using a nude mouse transplanted tumor model.Results: SOX8 expression was higher (P < 0.05) and miR-139 expression was lower (P < 0.05) in HCC1806 and BT549 cells than in MCF-10A cells. SOX8 overexpression significantly enhanced cell proliferation and migration, reduced the rate of cell apoptosis, and increased tumor sphere formation (P < 0.05) compared with the control group, whereas SOX8 knockdown had the opposite effect (P < 0.05). Overexpression of miR-139 markedly decreased cell proliferation and migration, increased cell apoptosis in vitro, and decreased tumor angiogenesis and volume in vivo (P < 0.05).Conclusion: miR-139 suppressed the tumorigenicity of TNBC cells by targeting SOX8.Keywords: breast cancer, carcinogenesis, molecular targets, gene regulationhttps://www.dovepress.com/microrna-139-suppresses-the-tumorigenicity-of-triple-negative-breast-c-peer-reviewed-article-CMARbreast cancercarcinogenesismolecular targetsgene regulation |
spellingShingle | Dong L Zhou D Xin C Liu B Sun P MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8 Cancer Management and Research breast cancer carcinogenesis molecular targets gene regulation |
title | MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8 |
title_full | MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8 |
title_fullStr | MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8 |
title_full_unstemmed | MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8 |
title_short | MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8 |
title_sort | microrna 139 suppresses the tumorigenicity of triple negative breast cancer cells by targeting sox8 |
topic | breast cancer carcinogenesis molecular targets gene regulation |
url | https://www.dovepress.com/microrna-139-suppresses-the-tumorigenicity-of-triple-negative-breast-c-peer-reviewed-article-CMAR |
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