Abstract 1547: LncRNA UCA1 modulates glucose metabolism proteins in colorectal cancer

Abstract

Abstract Colorectal cancer (CRC) is the primary cause of cancer-related deaths worldwide. According to the American Cancer Society, it is the third most common cancer diagnosed in adults in the United States. It will have an estimated 149,500 new cases of colon cancer in 2021. In addition, studies show CRC has increased morbidity with obesity and obesity-related diseases such as diabetes. In a geographical area of The Rio Grande Valley which has a high incidence of diabetes, understanding the connection between CRC and diabetes is essential. Our lab identified LncRNA UCA1, a poor prognosis marker in CRC, responsible for increased proliferation and upregulating glucose metabolic pathway. First, we investigated the possible role of UCA1 in glucose metabolism, finding that UCA1 overexpressing cells (SW480+UCA1) showed a higher glucose consumption than their vector. The inverse of this trend was established when we knockdown UCA1 (SW620+shUCA1). Further, we found that overexpressing UCA1 increases the migration, invasion, and proliferation of SW480 cells. A vital aspect of the metastatic progression is when the cell survives detachment from the extracellular matrix. A route in which they overcome apoptosis is through modulation of the metabolic pathways, upregulating such markers as GLUT1, FDFT1, SGK1, and HIF1α. At 36hrs of anchorage-independent stimulation, we found an uptick in glucose consumption and lactate production and an increase in the expression of GLUT1, FDFT1, SGK1, and HIF1α compared to 0hrs. The Warburg effect is when glycolysis is no longer connected to the tricarboxylic acid cycle or oxidative phosphorylation. The increase in expression of the markers GLUT1, FDFT1, SGK1, and HIF1α indicates aerobic metabolic activity during anchorage-independent growth with UCA1 expression. This relationship needs to be further examined and could lead to understanding the increased morbidity associated with diabetes and CRC. Citation Format: Sophia Leslie, Kyle Doxtater, Samantha Lopez, Adithya Anilkumar, Meena Jaggi, Subhash Chauhan, Manish Tripathi. LncRNA UCA1 modulates glucose metabolism proteins in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1547.