Qiao Qiao, Bai Ruixia, Song Wanying, Gao Haining, Zhang Minyu, Lu Jingkun, Hong Mei, Zhang Xuan, Sun Peng, Zhang Qian, Zhao Pengwei
Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia Medical University, No.1, Tongdao North Street, Huimin District, Hohhot, 010050, PR China.
Department of Clinical Laboratory, Inner Mongolia People's Hospital, Zhaowuda Road, Hohhot, 010018, PR China.
Exp Cell Res. 2021 Oct 15;407(2):112809. doi: 10.1016/j.yexcr.2021.112809. Epub 2021 Sep 3.
Defensins are highly conserved antimicrobial peptides, which ubiquitously expressed in different species. In addition to the functions in host defense, their aberrant expression have also been documented in cancerous tissue including breast cancer, lung caner and renal carcinoma etc. Whereas, roles of Defensin Alpha 5 (DEFA5) in colon cancer has not been explored. Bioinformatic analysis was used to study the expression of DEFA5 and its correlation with clinical outcomes; Western blot, qPCR, Co-immunoprecipitation, xenograft models were used to the study the molecular mechanism. Decreased expression of DEFA5 at protein level was observed in colon tissues. Colon cancer cell lines proliferation and colony formation capacity were significantly suppressed by DEFA5 overexpression. Moreover, in vivo tumor growth in nude mice was also suppressed by DEFA5 overexpression, suggesting a tumor suppressor role of DEFA5 in colon cancer. Mechanistically, DEFA5 directly binds to the subunits of PI3K complex, thus attenuates the downstream signaling transduction, leads to delayed cell growth and metastasis. Collectively, we concluded that DEFA5 showed an inhibitory effect in colon cancer cell growth and may serve as a potential tumor suppressor in colon cancer.
防御素是高度保守的抗菌肽，在不同物种中普遍表达。除了在宿主防御中的功能外，它们在包括乳腺癌、肺癌和肾癌等癌组织中的异常表达也有记录。然而，防御素α5（DEFA5）在结肠癌中的作用尚未被探索。本研究采用生物信息学分析方法研究DEFA5的表达及其与临床预后的相关性；运用蛋白质免疫印迹法、定量聚合酶链反应、免疫共沉淀、异种移植模型等研究其分子机制。在结肠组织中观察到DEFA5蛋白水平表达降低。DEFA5过表达显著抑制结肠癌细胞系的增殖和集落形成能力。此外，DEFA5过表达还抑制了裸鼠体内肿瘤的生长，提示DEFA5在结肠癌中具有肿瘤抑制作用。机制上，DEFA5直接与PI3K复合物的亚基结合，从而减弱下游信号转导，导致细胞生长和转移延迟。综上所述，我们得出结论，DEFA5对结肠癌细胞生长具有抑制作用，可能是结肠癌潜在的肿瘤抑制因子。
