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

J Chemother. 2021 Oct;33(6):409-419. doi: 10.1080/1120009X.2021.1906032. Epub 2021 Apr 5.


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; HK2; LDHA; glycolysis; lncRNA UCA1; paclitaxel resistance.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy
  • Drug Resistance, Neoplasm / physiology*
  • Glycolysis / drug effects*
  • Hexokinase / biosynthesis
  • Humans
  • L-Lactate Dehydrogenase / biosynthesis
  • Paclitaxel / pharmacology*
  • RNA, Long Noncoding / biosynthesis*


  • Antineoplastic Agents
  • RNA, Long Noncoding
  • UCA1 RNA, human
  • L-Lactate Dehydrogenase
  • LDHA protein, human
  • HK2 protein, human
  • Hexokinase
  • Paclitaxel