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长链非编码 RNA 尿路上皮癌相关 1 的过表达通过促进糖酵解导致结直肠癌细胞对紫杉醇(泰素)耐药。

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

机构信息

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.

出版信息

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

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.

摘要

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。

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