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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Main Authors: Dong L, Zhou D, Xin C, Liu B, Sun P
Format: Article
Language:English
Published: Dove Medical Press 2020-09-01
Series:Cancer Management and Research
Subjects:
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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