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TRIM59促进结直肠癌的增殖,并通过PI3K/AKT途径促进转移。

TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway.

作者信息

Sun Ye, Ji Bing, Feng Yifei, Zhang Yue, Ji Dongjian, Zhu Chunyan, Wang Sen, Zhang Chuan, Zhang Dongsheng, Sun Yueming

机构信息

Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

出版信息

Oncol Rep. 2017 Jul;38(1):43-52. doi: 10.3892/or.2017.5654. Epub 2017 May 22.

Abstract

Tripartite motif-containing 59 (TRIM59) belongs to the tripartite motif (TRIM) protein family and is upregulated in various malignancies. However, its expression in colorectal cancer (CRC) is still unknown. In the present study, we examined the expression and biological function of TRIM59 in CRC. We analyzed CRC tissues and cells by quantitative real-time polymerase chain reaction. Kaplan-Meier survival analysis was used to evaluate the prognostic significance of TRIM59 in CRC patients. Furthermore, we investigated the role of TRIM59 in CRC growth and metastasis. The potential mechanism underlying the regulation of cell metastasis by TRIM59 was determined by western blotting. TRIM59 expression was conspicuously overexpressed in CRC tissues and CRC cell lines compared to that noted in the corresponding normal control cells. Patients with higher TRIM59 expression had poorer prognosis. Furthermore, knockdown of TRIM59 suppressed cell proliferation through the induction of apoptosis and inhibited migration and invasion significantly in vitro. Further investigation revealed that knockdown of TRIM59 effectively reversed the expression of epithelial-mesenchymal transformation‑related proteins vimentin, Snail and E-cadherin. Our preliminary results confirm that TRIM59 can be mediated by PI3K/AKT signaling. TRIM59 functions as an oncogene in CRC progression, which could be a novel target for the detection and treatment of CRC.

摘要

含三联基序蛋白59(TRIM59)属于三联基序(TRIM)蛋白家族,在多种恶性肿瘤中表达上调。然而,其在结直肠癌(CRC)中的表达仍不清楚。在本研究中,我们检测了TRIM59在CRC中的表达及生物学功能。我们通过定量实时聚合酶链反应分析CRC组织和细胞。采用Kaplan-Meier生存分析评估TRIM59在CRC患者中的预后意义。此外,我们研究了TRIM59在CRC生长和转移中的作用。通过蛋白质印迹法确定TRIM59调控细胞转移的潜在机制。与相应的正常对照细胞相比,TRIM59在CRC组织和CRC细胞系中明显过表达。TRIM59表达较高的患者预后较差。此外,敲低TRIM59可通过诱导凋亡抑制细胞增殖,并在体外显著抑制迁移和侵袭。进一步研究表明,敲低TRIM59可有效逆转上皮-间质转化相关蛋白波形蛋白、Snail和E-钙黏蛋白的表达。我们的初步结果证实,TRIM59可由PI3K/AKT信号介导。TRIM59在CRC进展中起癌基因作用,可能是CRC检测和治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd40/5492839/73e6304adb7a/OR-38-01-0043-g00.jpg

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