Zhou Wei, Li Xingquan, Zhang Bolin, Peng Hong, Quan Chunyang, Xiao Xin, Luo Man, Huang Yanxiao, Xu Debin, Huang Kai, Jin Qifang, Lu Shan
Department of Abdominal Surgery, Jiangxi Cancer Hospital Nanchang 330029, Jiangxi, China.
Oncology Teaching and Research Office, The Second Affiliated Hospital of Nanchang Medical College Nanchang 330029, Jiangxi, China.
Am J Cancer Res. 2024 Jun 15;14(6):2852-2867. doi: 10.62347/EQDK1844. eCollection 2024.
Cholangiocarcinoma (CCA) is a common malignancy of the digestive system, and its treatment is greatly challenged by rising chemoresistance. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the development of drug resistance in tumors. However, the role of the lncRNA CCAT1 in erlotinib resistance in CCA remains unclear. In this investigation, we identified CCAT1 as a pivotal factor contributing to erlotinib resistance in CCA. Furthermore, we uncovered that lncRNA CCAT1 modulated epithelial-mesenchymal transition (EMT) through Rho-associated coiled-coil-forming protein kinase 2 (ROCK2), thereby conferring erlotinib resistance upon CCA cells. Mechanistically, we demonstrated that miR-181a-5p interacted with CCAT1 to modulate the expression of ROCK2. Collectively, these findings shed light on the significant role of CCAT1 in the development of erlotinib resistance in CCA. The functional suppression of CCAT1 holds promise in enhancing the sensitivity to erlotinib by reversing EMT through the miR-181a-5p/ROCK2 signaling pathway. These findings provide valuable insights into the mechanisms underlying erlotinib resistance in CCA and the potential strategies for its treatment.
胆管癌（CCA）是消化系统常见的恶性肿瘤，其治疗面临着化疗耐药性不断上升的巨大挑战。长链非编码RNA（lncRNA）已被证明在肿瘤耐药性发展中起关键作用。然而，lncRNA CCAT1在CCA对厄洛替尼耐药中的作用仍不清楚。在本研究中，我们确定CCAT1是导致CCA对厄洛替尼耐药的关键因素。此外，我们发现lncRNA CCAT1通过Rho相关卷曲螺旋形成蛋白激酶2（ROCK2）调节上皮-间质转化（EMT），从而赋予CCA细胞厄洛替尼耐药性。机制上，我们证明miR-181a-5p与CCAT1相互作用以调节ROCK2的表达。总体而言，这些发现揭示了CCAT1在CCA对厄洛替尼耐药发展中的重要作用。CCAT1的功能抑制有望通过miR-181a-5p/ROCK2信号通路逆转EMT来增强对厄洛替尼的敏感性。这些发现为CCA中厄洛替尼耐药的潜在机制及其治疗策略提供了有价值的见解。
