Expression of Long Noncoding RNA YIYA Promotes Glycolysis in Breast Cancer
Abstract
Long noncoding RNA (lncRNA) is yet to be linked to cancer metabolism. Here, we report that upregulation of the lncRNA LINC00538 (YIYA) promotes glycolysis, cell proliferation, and tumor growth in breast cancer. YIYA is associated with the cytosolic cyclin-dependent kinase CDK6 and regulated CDK6-dependent phosphorylation of the fructose bisphosphatase PFK2 (PFKFB3) in a cell-cycle–independent manner. In breast cancer cells, these events promoted catalysis of glucose 6-phosphate to fructose-2,6-bisphosphate/fructose-1,6-bisphosphate. CRISPR/Cas9-mediated deletion of YIYA or CDK6 silencing impaired glycolysis and tumor growth in vivo. In clinical specimens of breast cancer, YIYA was expressed in approximately 40% of cases where it correlated with CDK6 expression and unfavorable survival outcomes. Our results define a functional role for lncRNA in metabolic reprogramming in cancer, with potential clinical implications for its therapeutic targeting.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 14, 2018
- Source ID
- 10.1158/0008-5472.can-17-0385
Entities
People
- Arun Sreekumar
- Chunlai Li
- Chunru Lin
- Cristian Coarfa
- David H Hawke
- Feng Jin
- Haoqiang Ying
- Jeffrey R. Marks
- Jianwei Zhou
- Ke Liang
- Leng Han
- Liang Yan
- Liuqing Yang
- Mien-Chie Hung
- Nagireddy Putluri
- Peter K. Park
- Qingsong Hu
- Shouyu Wang
- Tina K. Nguyen
- Vasanta Putluri
- Yan Zhou
- Yanyan Zhang
- Yu Xiang
- Zhen Xing
Organizations
- American Cancer Society
- Baylor College of Medicine
- Cancer Prevention and Research Institute of Texas
- China Medical University
- Duke University
- Nanjing Medical University
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health
- United States Department of Defense
- University of Texas Health Science Center at Houston
- University of Texas at Austin