Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
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.
一些结直肠癌患者对包括紫杉醇在内的常规化疗药物表现出耐药性。本研究探讨了长链非编码 RNA 尿路上皮癌相关 1（UCA1）在调节人结直肠癌细胞紫杉醇耐药中的作用。根据我们的结果，UCA1 在结肠癌细胞系/组织中明显上调。构建 UCA1 过表达载体表明，高 UCA1 表达是紫杉醇耐药的原因，紫杉醇可以诱导 UCA1 表达。重要的是，紫杉醇耐药细胞的糖酵解率高于紫杉醇敏感细胞，且关键糖酵解酶己糖激酶 2（HK2）和乳酸脱氢酶 A（LDHA）的表达上调。进一步的研究表明，UCA1 可以通过调节 HK2 和 LDHA 的表达直接调节糖酵解，从而促进紫杉醇耐药。UCA1 是克服结直肠癌化疗耐药的潜在靶点。我们报告了 UCA-1 调节的糖酵解的调节作为一种新的抗癌策略，以及 UCA1 在紫杉醇耐药中的新作用。
