CircRNA RNA hsa_circ_0008234 Promotes Colon Cancer Progression by Regulating the miR-338-3p/ETS1 Axis and PI3K/AKT/mTOR Signaling

被引:10
|
作者
Wu, Dejun [1 ,2 ]
Li, Yuqin [3 ]
Xu, Anjun [1 ]
Tang, Wenqing [4 ]
Yu, Bo [5 ,6 ]
机构
[1] Fudan Univ, Shanghai Pudong Hosp, Pudong Med Ctr, Dept Gen Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China
[2] Fudan Univ, Shanghai Pudong Hosp, Pudong Med Ctr, Dept Gastrointestinal Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China
[3] Fudan Univ, Shanghai Pudong Hosp, Pudong Med Ctr, Dept Gastroenterol, 2800 Gongwei Rd, Shanghai 201399, Peoples R China
[4] Fudan Univ, Zhongshan Hosp, Shanghai Inst Liver Dis, Dept Gastroenterol & Hepatol, Shanghai 201399, Peoples R China
[5] Fudan Univ, Shanghai Pudong Hosp, Pudong Med Ctr, Vasc Surg Dept, 2800 Gongwei Rd, Shanghai 201399, Peoples R China
[6] Shanghai Key Lab Vasc Les Regulat & Remodeling, Shanghai 201399, Peoples R China
关键词
colon cancer; hsa_circ_0008234; miR-338-3p; ETS1; PI3K; EPITHELIAL-MESENCHYMAL TRANSITION; CELL-PROLIFERATION; TARGETING ETS1; METASTASIS; BIOGENESIS; MIGRATION;
D O I
10.3390/cancers15072068
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Circular RNAs (circRNAs) have been shown to play a crucial role in cancer occurrence and progression. This present work investigated the link between hsa_circ_0008234 and colon cancer. Data retrieved from GSE172229 was used to compare the circRNA profiles of colon cancer and surrounding non-tumorous tissues. The amount of RNA and protein in the molecules was determined using quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The cell proliferation ability was assessed using CCK8, EdU, colon formation, and nude mice tumorigenesis tests. Cell invasion and migration abilities were evaluated using transwell wound healing and mice lung metastasis model. Hsa_circ_0008234 piqued our interest because bioinformatics and qRT-PCR analyses revealed that it is upregulated in colon cancer tissue. Cell phenotypic studies suggest that hsa_circ_0008234 may significantly increase colon cancer cell aggressiveness. Mice experiments revealed that inhibiting hsa_circ_0008234 significantly reduced tumor growth and metastasis. Moreover, the fluorescence in situ hybridization experiment demonstrated that hsa_circ_0008234 is primarily found in the cytoplasm, implying that it potentially functions via a competitive endogenous RNA pathway. These findings indicated that hsa_circ_0008234 may act as a "molecular sponge" for miR-338-3p, increasing the expression of miR-338-target 3p's ETS1. In addition, the traditional oncogenic pathway PI3K/AKT/mTOR signaling was found to be the potential downstream pathway of the hsa_circ_0008234/miR-338-3p/ETS1 axis. In conclusion, hsa_circ_0008234 increases colon cancer proliferation, infiltration, and migration via the miR-338-3p/ETS1/PI3K/AKT axis; therefore, it could serve as a target and a focus for colon cancer therapy.
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页数:16
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