A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth

Qiang Li; Xiao Wang; Liheng Zhou; Mingyun Jiang; Guansheng Zhong; Shuguang Xu; Minjun Zhang; Yigan Zhang; Xiaodong Liang; Lei Zhang; Jianming Tang; Haibo Zhang

doi:10.3389/fonc.2021.619915

A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth

Front Oncol. 2021 Mar 26:11:619915. doi: 10.3389/fonc.2021.619915. eCollection 2021.

Authors

Qiang Li¹, Xiao Wang², Liheng Zhou³, Mingyun Jiang⁴, Guansheng Zhong⁵, Shuguang Xu³, Minjun Zhang⁴, Yigan Zhang⁶, Xiaodong Liang¹, Lei Zhang⁷, Jianming Tang⁸, Haibo Zhang¹

Affiliations

¹ Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
² Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
³ Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Graduate Department, Bengbu Medical College, Bengbu, China.
⁵ Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁶ The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.
⁷ Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁸ Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, China.

Abstract

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity in vitro and in vivo. Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.

Keywords: KLF5; breast cancer; cell proliferation; lncRNA LINC00152; positive feedback loop.