Oncogenic lncRNA LINC00973 promotes Warburg effect by enhancing LDHA enzyme activity

Huili Wang; Kequan Lin; Lin Zhu; Shaojun Zhang; Le Li; Yilie Liao; Baichao Zhang; Ming Yang; Xinde Liu; Lu Li; Shasha Li; Liuqing Yang; Haiyan Wang; Qianyu Wang; Haitao Li; Suneng Fu; Xiaorong Zhang; Peng Jiang; Qiangfeng Cliff Zhang; Jing Cheng; Dong Wang

doi:10.1016/j.scib.2021.01.001

Oncogenic lncRNA LINC00973 promotes Warburg effect by enhancing LDHA enzyme activity

Sci Bull (Beijing). 2021 Jul 15;66(13):1330-1341. doi: 10.1016/j.scib.2021.01.001. Epub 2021 Jan 5.

Authors

Huili Wang¹, Kequan Lin², Lin Zhu², Shaojun Zhang², Le Li², Yilie Liao², Baichao Zhang², Ming Yang¹, Xinde Liu², Lu Li², Shasha Li¹, Liuqing Yang², Haiyan Wang¹, Qianyu Wang², Haitao Li¹, Suneng Fu², Xiaorong Zhang³, Peng Jiang², Qiangfeng Cliff Zhang², Jing Cheng⁴, Dong Wang⁵

Affiliations

¹ School of Medicine, Tsinghua University, Beijing 100084, China.
² School of Life Sciences, Tsinghua University, Beijing 100084, China.
³ Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
⁴ School of Medicine, Tsinghua University, Beijing 100084, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China; Center for Precision Medicine, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: jcheng@tsinghua.edu.cn.
⁵ School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: dwang@cdutcm.edu.cn.

PMID: 36654155
DOI: 10.1016/j.scib.2021.01.001

Abstract

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer and essential for metabolism in malignancies, but its regulation and modulation in cancer cells remain poorly understood. Here, using large-scale functional screening, we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973. Notably, knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo. Mechanistically, LINC00973 directly binds to lactate dehydrogenase A (LDHA), an essential glycolytic enzyme, and enhances its enzymatic activity, thereby promoting glycolysis. Clinically, high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers. This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect, and may represent a potential target for broad-acting anti-cancer therapies.

Keywords: Biomarker; Cancer metabolism; LDHA; LINC00973; Warburg effect.