DGUOK-AS1 acts as a tumorpromoter through regulatingmiR-204-5p/IL-11 axis in breast cancer

Yiran Liang; Fangzhou Ye; Yajie Wang; Yalun Li; Yaming Li; Xiaojin Song; Dan Luo; Li Long; Dianwen Han; Ying Liu; Zekun Wang; Bing Chen; Wenjing Zhao; Lijuan Wang; Qifeng Yang

Molecular Therapy: Nucleic Acids (Dec 2021)

DGUOK-AS1 acts as a tumorpromoter through regulatingmiR-204-5p/IL-11 axis in breast cancer

Yiran Liang,
Fangzhou Ye,
Yajie Wang,
Yalun Li,
Yaming Li,
Xiaojin Song,
Dan Luo,
Li Long,
Dianwen Han,
Ying Liu,
Zekun Wang,
Bing Chen,
Wenjing Zhao,
Lijuan Wang,
Qifeng Yang

Affiliations

Yiran Liang: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Fangzhou Ye: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Yajie Wang: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Yalun Li: Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
Yaming Li: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Xiaojin Song: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Dan Luo: Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Li Long: Department of Breast Surgery, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China
Dianwen Han: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Ying Liu: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Zekun Wang: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China
Bing Chen: Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Wenjing Zhao: Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Lijuan Wang: Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Qifeng Yang: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China; Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China; Research Institute of Breast Cancer, Shandong University, Jinan, Shandong 250012, P.R. China; Corresponding author: Qifeng Yang, PhD, MD, Department of Breast Surgery, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, Shandong 250012, P.R. China.

Journal volume & issue: Vol. 26
pp. 1079 – 1091

Abstract

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Breast cancer is one of the most lethal malignancies among women; however, the underlying molecular mechanism involved in the progression and metastasis of breast cancer remains unclear. Numerous studies have confirmed that long noncoding RNAs are abnormally expressed in breast cancer and play crucial roles in cell proliferation and metastasis. In the study, we evaluated the functional role and detailed mechanism of DGUOK-AS1 in breast cancer progression and metastasis. DGUOK-AS1 knockdown suppressed proliferation, migration, and invasion of breast cancer cells in vitro and in vivo. Mechanistically, miR-204-5p was identified as an inhibitory target of DGUOK-AS1, which served as a tumor suppressor in breast cancer. Significantly, we found that the ectopic expression of miR-204-5p could counteract DGUOK-AS1-mediated promotion of cell proliferation and metastasis in breast cancer. Moreover, IL-11 was found to be the downstream target of miR-204-5p, and DGUOK-AS1 could protect IL-11 from miR-204-5p-mediated degradation. DGUOK-AS1 overexpression promoted breast cancer cell migration, angiogenesis, and macrophage migration, mediating by the increased secretion of IL-11, which was extremely important for cancer progression. Collectively, our studies reveal that DGUOK-AS1/miR-204-5p/IL-11 axis plays a significant role in the progression and metastasis of breast cancer, and DGUOK-AS1 might be a novel biomarker and therapeutic target for breast cancer.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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