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C2ORF68 与人结直肠癌中 HuR 的相互作用。

Interaction between C2ORF68 and HuR in human colorectal cancer.

机构信息

Department of Human Anatomy, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

出版信息

Oncol Rep. 2019 Mar;41(3):1918-1928. doi: 10.3892/or.2019.6973. Epub 2019 Jan 21.

Abstract

The detailed molecular mechanisms underlying the carcinogenesis of colorectal carcinoma (CRC) remain unknown. Therefore, the present study was designed to investigate the effect of the relationship between C2ORF68 and HuR in regards to the carcinogenesis of CRC. Immunohistochemistry, immunofluorescence, flow cytometry, Transwell migration and CCK‑8 assays, co‑immunoprecipitation, qRT‑PCR and western blot analysis were performed. The results revealed that expression of C2ORF68 was significantly upregulated in the cytoplasm and nucleus in rectal cancer, and upregulation of the expression of C2ORF68 was associated with lymph node metastasis and pathological grade. C2ORF68 and HuR were found to be mainly localized in the nucleus in both SW480 and LoVo cells. In LoVo+c2orf68,‑HuR and LoVo+c2orf68 cells, the cell apoptosis rate was significantly decreased, cell proliferation rate was significantly increased, and the cell migration rate was only significantly increased in the LoVo+c2orf68 cells. In SW480‑c2orf68,‑HuR, SW480‑c2orf68 and SW480‑HuR, the cell apoptosis rate was significantly increased. At the same time, cell proliferation and the cell migration rate were significantly decreased. The mRNA and protein expression levels of C2orf68, HuR, Bcl‑2, c‑Myc, cyclin D and cyclin A were upregulated, while the expression of Bax was downregulated in LoVo+c2orf68 and LoVo+c20rf68,‑HuR cells. Expression levels of C2orf68, HuR, Bcl‑2, c‑Myc, cyclin D and cyclin A were downregulated while Bax was upregulated in the SW480‑c2orf68,‑HuR, SW480‑c2orf68 and SW480‑HuR cells. In conclusion, it is suggested that c2orf68 is a potential carcinogenesis factor in rectal cancer. Furthermore, c2orf68 may have a synergistic effect with HuR in the onset and development of CRC.

摘要

结直肠癌(CRC)发生的确切分子机制尚不清楚。因此,本研究旨在探讨 C2ORF68 与 HuR 之间的关系在 CRC 发生中的作用。进行了免疫组织化学、免疫荧光、流式细胞术、Transwell 迁移和 CCK-8 测定、共免疫沉淀、qRT-PCR 和 Western blot 分析。结果显示,C2ORF68 在直肠癌中的细胞质和细胞核中表达明显上调,C2ORF68 表达上调与淋巴结转移和病理分级相关。在 SW480 和 LoVo 细胞中,C2ORF68 和 HuR 主要定位于细胞核。在 LoVo+c2orf68- HuR 和 LoVo+c2orf68 细胞中,细胞凋亡率显著降低,细胞增殖率显著增加,而 LoVo+c2orf68 细胞的细胞迁移率仅显著增加。在 SW480-c2orf68-HuR、SW480-c2orf68 和 SW480-HuR 中,细胞凋亡率显著增加。同时,细胞增殖和细胞迁移率显著降低。LoVo+c2orf68 和 LoVo+c2orf68-HuR 细胞中 C2orf68、HuR、Bcl-2、c-Myc、cyclin D 和 cyclin A 的 mRNA 和蛋白表达水平上调,而 Bax 的表达下调。SW480-c2orf68-HuR、SW480-c2orf68、SW480-c2orf68 和 SW480-HuR 细胞中 C2orf68、HuR、Bcl-2、c-Myc、cyclin D 和 cyclin A 的表达水平下调,而 Bax 的表达上调。总之,提示 c2orf68 是直肠癌潜在的致癌因素。此外,c2orf68 可能与 HuR 在 CRC 的发生和发展中具有协同作用。

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