Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, P.R. China.
Int J Biol Sci. 2022 Sep 21;18(15):5787-5808. doi: 10.7150/ijbs.76096. eCollection 2022.
Circular RNAs (CircRNAs) have attracted a growing interest of research in cancer. The regulatory roles and mechanisms of circRNAs in progression, metastasis and drug resistance of esophageal squamous cell carcinoma (ESCC) needed to be clarified. Our previous study revealed the crucial role of Apatinib in ESCC therapy. However, the correlation between circRNAs and Apatinib resistance remained unclear. 3 pairs of tumor and paracancerous tissues of ESCC patients were used for RNA sequencing. Western blot analysis, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, apoptosis and animal assays were conducted to confirm the roles and specific mechanisms of hsa_circ_0003823 as well as the effects of it on Apatinib sensitivity in ESCC. Our results revealed that hsa_circ_0003823 was highly expressed in ESCC and associated with poor prognosis. Further results indicated that hsa_circ_0003823 promoted proliferation and metastasis ability of ESCC. In the section of mechanism experiments, hsa_circ_0003823 regulated CRISP3 by targeting microRNA-607 (miR-607) to promote progression of ESCC. Besides, we found that silencing hsa_circ_0003823 improved Apatinib sensitivity. hsa_circ_0003823 resulted in Apatinib resistance by miR-607/CRISP3 axis. In this study, we elucidated the function of hsa_circ_0003823 and its role in promoting tumor progression, metastasis and Apatinib resistance of ESCC through miR-607/CRISP3 axis.
环状 RNA（CircRNAs）在癌症研究中引起了越来越多的关注。环状 RNA 在食管鳞状细胞癌（ESCC）进展、转移和耐药中的调控作用和机制需要阐明。我们之前的研究表明阿帕替尼在 ESCC 治疗中的重要作用。然而，环状 RNA 与阿帕替尼耐药之间的相关性尚不清楚。
使用 3 对 ESCC 患者的肿瘤和癌旁组织进行 RNA 测序。通过 Western blot 分析、RNA 免疫沉淀（RIP）、双荧光素酶报告基因测定、凋亡和动物实验，证实了 hsa_circ_0003823 的作用及其对 ESCC 中阿帕替尼敏感性的具体机制，以及其对阿帕替尼敏感性的影响。
我们的结果表明，hsa_circ_0003823 在 ESCC 中高表达，与预后不良相关。进一步的结果表明，hsa_circ_0003823 促进了 ESCC 的增殖和转移能力。在机制实验部分，hsa_circ_0003823 通过靶向 microRNA-607（miR-607）来调节 CRISP3，从而促进 ESCC 的进展。此外，我们发现沉默 hsa_circ_0003823 可以提高阿帕替尼的敏感性。hsa_circ_0003823 通过 miR-607/CRISP3 轴导致阿帕替尼耐药。
在这项研究中，我们通过 miR-607/CRISP3 轴阐明了 hsa_circ_0003823 的功能及其在促进 ESCC 肿瘤进展、转移和阿帕替尼耐药中的作用。
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