Overexpression of Long Non-Coding RNA Urothelial Carcinoma Associated 1 (LncRNA UCA1) Affects Paclitaxel (Taxol) Resistance in Colorectal Cancer Cells through the Promotion of Glycolysis

Xiang-liang Zhang, Tian-tian Zhen, Yu Dong and Hui-juan Shi

Department of Abdominal Surgery, The Affiliated Hospital of Guangzhou Medical University, China
Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, China
Both authors equal contributed

^*Correspondance to: Hui-juan Shi 

 PDF  Full Text DOI: 10.25107/2474-1647.2262

Abstract

Purpose: Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) have critical roles in the regulation of cancer progression. Colorectal cancer is one of the most common malignancies of human. However, a significant fraction of colorectal cancer shows resistance to conventional chemotherapeutic agents such as Taxol. In this study, we investigate the roles of lncRNA urothelial carcinoma associated 1 (UCA1) in the modulation of Taxol resistance in human colorectal cancer cells.Methods: UCA1 is significantly up-regulated in both colon cancer cell lines and tissues compared with normal colon cell lines or adjacent tissues. Through the construction of UCA1 overexpression vector, it is found that high UCA1 expression was better for Taxol resistance, and we also confirm that Taxol can induce UCA1 expression. Importantly, the rates of glucose consumption, lactate production, and extracellular acidification in Taxol resistant colorectal cancer cells are obviously higher than those in Taxol-sensitive cells. The glycolysis key enzymes Hexokinase 2 (HK2) and Lactate Dehydrogenase A (LDHA) are significantly up-regulated in Taxol-resistant cells. The survival rate of cancer cells is decreased when treated with HK2 and LDHA inhibitors.
Results: UCA1 can directly regulate glycolysis: overexpression of UCA1 promotes glycolysis whereas knockdown of UCA1 by siRNA suppresses glycolysis. We also demonstrate that the survival rate of colorectal cancer cells is increased by UCA1 knockdown by siRNA after the addition of HK2 and decreased by UCA1 overexpression after the addition of HK2 inhibitor.
Conclusion: Our study provides mechanisms for the UCA1-modulated chemo resistance and thus represents a potential long non-coding target to overcome chemo resistance in colorectal cancer, which provides a new target of chemo resistant drugs for colorectal cancer patients.

Keywords

Colorectal cancer; LncRNA UCA1; Paclitaxel resistance; Glycolysis

Cite the article

Xiang-liang Zhang, Tian-tian Zhen, Dong Y, Hui-juan Shi. Overexpression of Long Non-Coding RNA Urothelial Carcinoma Associated 1 (LncRNA UCA1) Affects Paclitaxel (Taxol) Resistance in Colorectal Cancer Cells through the Promotion of Glycolysis. Clin Surg. 2018; 3: 2262.