Int J Biol Sci 2022; 18(15):5787-5808. doi:10.7150/ijbs.76096 This issue
1. Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
2. Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, P.R. China.
3. Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
* These authors contributed equally to this work.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: hsa_circ_0003823, miR-607, crisp3, apatinib, esophageal squamous cell carcinoma