Oncogenic lncRNA LINC00973 promotes warburg effect by enhancing LDHA enzyme activity

Abstract Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer and essential for malignancies, but its regulation and modulation in cancer cells remain poorly understood. Here, by large-scale functional screening, we screened out 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 enzyme activity, thereby promoting glycolysis. 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.