| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Ling, Min Li, Jun Liu, Qizhan Lu, Lu Liu, Xinlu Luo, Fei Shi, Le Lu, Xiaolin Zhang, Aihua |
| Description |
Author Affiliation: Luo F ( Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China); Liu X ( Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China); Ling M ( Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China.); Lu L ( Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China); Shi L ( Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China); Lu X ( Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China); Li J ( The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guiyang Medical University, Guiyang 550025, Guizhou, People's Republic of China.); Zhang A ( The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guiyang Medical University, Guiyang 550025, Guizhou, People's Republic of China.); Liu Q ( Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China) |
| Abstract |
Accelerated glycolysis, a common process in tumor cells called the Warburg effect, is associated with various biological phenomena. However, the role of glycolysis induced by arsenite, a well-established human carcinogen, is unknown. Long non-coding RNAs (lncRNAs) act as regulators in various cancers, but how lncRNAs regulate glucose metabolism remains largely unexplored. We have found that, in human hepatic epithelial (L − 02) cells, arsenite increases lactate production; glucose consumption; and expression of glycolysis-related genes, including HK-2 , Eno-1 , and Glut-4 . In L-02 cells exposed to arsenite, the lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and hypoxia inducible factors (HIFs)-α, the transcriptional regulators of cellular response to hypoxia, are over-expressed. In addition, HIF-1α, not HIF-2α, is involved in arsenite-induced glycolysis, and MALAT1 enhances arsenite-induced glycolysis. Although MALAT1 regulates HIF-α and promotes arsenite-induced glycolysis, MALAT1 promotes glycolysis through HIF-1α, not HIF-2α. Moreover, arsenite-increased MALAT1 enhances the disassociation of Von Hippel–Lindau (VHL) tumor suppressor from HIF-1α, alleviating VHL-mediated ubiquitination of HIF-1α, which causes accumulation of HIF-1α. In sum, these findings indicate that MALAT1, acting through HIF-1α stabilization, is a mediator that enhances glycolysis induced by arsenite. These results provide a link between the induction of lncRNAs and the glycolysis in cells exposed to arsenite, and thus establish a previously unknown mechanism for arsenite-induced hepatotoxicity. |
| ISSN |
00063002 |
| Journal |
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number |
9 |
| Volume Number |
1862 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2016-09-01 |
| Publisher Place |
Netherlands |
| Access Restriction |
Open |
| Subject Keyword |
Biochemistry |
| Content Type |
Text |
| Resource Type |
Article |
