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，它们在癌组织中的异常表达也被记录在案，包括乳腺癌、肺癌和肾癌等。然而，防御素 Alpha 5 (DEFA5) 在结肠癌中的作用尚未被探索。采用生物信息学分析DEFA5的表达及其与临床结局的相关性；Western印迹、qPCR、共免疫沉淀、异种移植模型被用于研究分子机制。在结肠组织中观察到 DEFA5 在蛋白质水平上的表达降低。DEFA5过表达显着抑制了结肠癌细胞系的增殖和集落形成能力。此外，体内DEFA5 过表达也抑制了裸鼠中的肿瘤生长，表明 DEFA5 在结肠癌中具有肿瘤抑制作用。从机制上讲，DEFA5 直接与 PI3K 复合体的亚基结合，从而减弱下游信号转导，导致细胞生长和转移延迟。总的来说，我们得出结论，DEFA5 在结肠癌细胞生长中显示出抑制作用，并且可能作为结肠癌的潜在肿瘤抑制因子。