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.

Graphical abstract

Through a large-scale functional screening, we identified a long non-coding RNA LINC00973 that is highly expressed in many types of human cancers and can significantly promote tumor cell proliferation in vitro and in vivo. Mechanistically, LINC00973 can bind to the key glycolysis enzyme LDHA (lactate dehydrogenase A) and enhance its enzyme activity, thereby accelerating the aerobic glycolysis of tumor cells, and ultimately promoting tumor cell proliferation. Clinically, high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers. Together, our work demonstrated that LINC00973 modulates a cancer-specific regulation mechanism for the Warburg effect and suggested a potential target against one of cancer’s vulnerabilities for developing broad-acting anti-cancer therapies.

For full text, please click https://www.sciencedirect.com/science/article/abs/pii/S2095927321000013#!

Introduction to Professor Dong Wang

Dong Wang received his Ph.D. degree in Biology from Tsinghua University in 2004 and then continued his scientific research at the University of California, San Diego as a postdoctoral researcher. In 2012, he joined the faculty of the School of Medicine, Tsinghua University. In 2018, he joined the School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine as a full professor. His research covers the study of mechanisms underlying gene expression and transcriptional reprogramming in cancer cells, and the identification of anti-cancer compounds by high throughput sequencing-based high throughput screening technology.