Theses and Dissertations

The Role of LncRNA UCA1 in Colorectal Cancer progression and metastasis

Sophia Michelle Leslie, The University of Texas Rio Grande Valley

Copyright 2023 The Author. All Rights Reserved.

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. Additionally, studies show CRC has increased morbidity with obesity and obesity-related diseases such as diabetes. In the geographical area of The Rio Grande Valley which has a high incidence of diabetes, understanding the connection between CRC and diabetes is essential. In our lab, we have 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). 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, lactate production, and an increase in the expression of metabolic markers compared to 0hrs. The increase in expression of these markers 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