Gao Xuefeng, Yin Junfeng, Yao Ying
Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225000, China.
Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu 225000, China.
J Oncol. 2022 May 11;2022:4288474. doi: 10.1155/2022/4288474. eCollection 2022.
Hsa_circ_0001955 presents significant upregulation in colorectal cancer (CRC) tissues. However, its role in CRC remains unclear. Thus, we attempted to clarify functions of hsa_circ_0001955 on CRC.
qRT-PCR was performed to examine hsa_circ_0001955, miR-583, and FGF21 levels. Western blotting was conducted to measure FGF21 protein expression. CCK-8, flow cytometry, and Ki-67 immunohistochemical staining and TUNEL assays were conducted to assess proliferation and apoptosis and , respectively. Cell invasion and migration were assessed by Transwell assay. Tumor-bearing mouse model and HE staining were used to assess inflammatory injury. Luciferase reporter system and RNA pull-down were conducted to evaluate the regulation between miR-583 and hsa_circ_0001955 or FGF21.
We found that hsa_circ_0001955 showed characteristics of upregulated circRNA in CRC. Further analysis indicated that hsa_circ_0001955 elevation facilitated CRC cell malignancy and promoted tumor growth . Furthermore, hsa_circ_0001955 was a miR-583 sponge and FGF21 was directly targeted by miR-583. In addition, we found that downregulation of miR-583 promoted hsa_circ_0001955-mediated CRC cell malignancy . In contrast, FGF21 elevation promoted miR-583-regulated CRC cell malignancy .
We demonstrated that hsa_circ_0001955 facilitated CRC progression via miR-583/FGF21 axis, suggesting that hsa_circ_0001955 may provide a novel insight for therapy of CRC.
hsa_circ_0001955在结直肠癌(CRC)组织中呈显著上调。然而,其在CRC中的作用仍不清楚。因此,我们试图阐明hsa_circ_0001955对CRC的作用。
采用qRT-PCR检测hsa_circ_0001955、miR-583和FGF21水平。进行蛋白质免疫印迹法检测FGF21蛋白表达。分别采用CCK-8、流式细胞术、Ki-67免疫组织化学染色和TUNEL法评估增殖和凋亡。通过Transwell实验评估细胞侵袭和迁移。采用荷瘤小鼠模型和苏木精-伊红(HE)染色评估炎症损伤。利用荧光素酶报告系统和RNA下拉实验评估miR-583与hsa_circ_0001955或FGF21之间的调控关系。
我们发现hsa_circ_0001955在CRC中表现为上调的环状RNA特征。进一步分析表明,hsa_circ_0001955升高促进了CRC细胞的恶性程度并促进肿瘤生长。此外,hsa_circ_0001955是miR-583的海绵,FGF21是miR-583的直接靶标。此外,我们发现miR-583下调促进了hsa_circ_0001955介导的CRC细胞恶性程度。相反,FGF21升高促进了miR-583调控的CRC细胞恶性程度。
我们证明hsa_circ_0001955通过miR-583/FGF21轴促进CRC进展,提示hsa_circ_0001955可能为CRC治疗提供新的见解。