Overexpression of long non-coding RNA urothelial carcinoma associated 1 causes paclitaxel (Taxol) resistance in colorectal cancer cells by promoting glycolysis

Abstract

Some colorectal cancer patients show resistance to conventional chemotherapeutic agents including Taxol. This study investigated the roles of lncRNA urothelial carcinoma-associated 1 (UCA1) in the modulation of Taxol resistance in human colorectal cancer cells. According to our results, UCA1 was significantly upregulated in colon cancer cell lines/tissues. Construction of the UCA1 overexpression vector revealed that high UCA1 expression was responsible for Taxol resistance and that Taxol can induce UCA1 expression. Importantly, Taxol-resistant cells had a higher glycolysis rate and upregulated expression of the key glycolysis enzymes hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA) than Taxol-sensitive cells. Further research demonstrated that UCA1 could directly regulate glycolysis by regulating HK2 and LDHA expression, which contributes to Taxol resistance. UCA1 is a potential target to overcome chemoresistance in colorectal cancer. We report the modulation of UCA-1-regulated glycolysis as a novel anticancer strategy along with the novel role of UCA1 in Taxol resistance.

Keywords:

• Colorectal cancer
• lncRNA UCA1
• paclitaxel resistance
• glycolysis
• HK2
• LDHA

Acknowledgements

We would thank for all people who had contributed to our research.

Disclosure statement

All authors declare that they have no conflicts of interest.

Notes on contributor

Huijuan Shi (MD, PHD) is a pathobiology and clinical oncology specialist at The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Kejun Li is MA student of clinical oncology and Research Trainees at Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.

Jinxin Feng, Master of clinical surgery and Research Trainees at Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.

Xiangliang Zhang (MD, PHD) is a general surgery and clinical oncology specialist at Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.

Author contributions

SHJ and LKJ designed the research; LKJ, FJX performed research and analyzed the data; Xiang-liang Zhang wrote and edited the manuscript.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Patient consent for publication

Written informed consents were obtained from all patients.

Additional information

Funding

This study was funded by China Scholarship Council (CSC) and the funding from the Guangdong Province Natural Science Funds (2017A030313763), the Guangzhou science and tecnology plan project (NO.201607010129, NO. 202002030292) and Funds for the construction of talents in high-level universities of Guangzhou Medical University (B195002004019).