敲除SIRT4可降低结肠癌细胞对5-氟尿嘧啶的化疗敏感性。
Knockout of SIRT4 decreases chemosensitivity to 5-FU in colorectal cancer cells.
作者信息
Zhu Yuanyuan, Wang Guangyu, Li Xiaobo, Wang Tianzhen, Weng Mingjiao, Zhang Yanqiao
机构信息
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
出版信息
Oncol Lett. 2018 Aug;16(2):1675-1681. doi: 10.3892/ol.2018.8850. Epub 2018 May 31.
Previous studies demonstrated that sirtuin (SIRT) 4 is aberrantly expressed in human malignant tumors and is associated with poor prognosis in patients with colorectal cancer. However, the role of SIRT4 in the progression of human colorectal cancer (CRC) and in chemotherapy remains unclear. In the present study, the expression of SIRT4 in CRC tissues and the effect of SIRT4 on colorectal cancer proliferation, migration and invasion was investigated. Additionally, the effects of SIRT4 on the chemosensitivity in colorectal cancer cells and the underlying molecular mechanisms were also explored. The results demonstrated that SIRT4 expression is significantly downregulated in CRC tissues and cell lines. Downregulation of SIRT4 significantly increased tumor proliferation, migration and invasion. Additionally, downregulation of SIRT4 decreased the chemosensitivity of CRC cells by inhibiting cell apoptosis. Thus, these results suggest that SIRT4 may be a promising therapeutic target in CRC.
先前的研究表明，沉默调节蛋白（SIRT）4在人类恶性肿瘤中表达异常，且与结直肠癌患者的不良预后相关。然而，SIRT4在人类结直肠癌（CRC）进展及化疗中的作用仍不清楚。在本研究中，我们调查了SIRT4在CRC组织中的表达情况以及SIRT4对结直肠癌增殖、迁移和侵袭的影响。此外，还探究了SIRT4对结直肠癌细胞化疗敏感性的影响及其潜在分子机制。结果表明，SIRT4在CRC组织和细胞系中的表达显著下调。SIRT4的下调显著增加了肿瘤的增殖、迁移和侵袭。此外，SIRT4的下调通过抑制细胞凋亡降低了结直肠癌细胞的化疗敏感性。因此，这些结果表明SIRT4可能是CRC中一个有前景的治疗靶点。
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