Dipartimento di Biopatologia e Biotecnologie Mediche, Sezione di Biologia e Genetica, University of Palermo, Palermo, Italy.
Department of Surgical, Oncological and Stomatological Disciplines, Sector of Clinical Research in Oral Medicine, University of Palermo, Palermo, Italy.
J Exp Clin Cancer Res. 2018 Apr 13;37(1):82. doi: 10.1186/s13046-018-0753-z.
Our previous study demonstrates that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability, and that this effect is associated with the downregulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on the contribution of DDHD1 in neurological disorders, there is no information on its role in cancer. This study investigates the role of DDHD1 in colon cancer.
DDHD1 siRNAs and an overexpression vector were transfected into colorectal cancer and normal cells to downregulate or upregulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics using SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells.
The results indicate that DDHD1 supports colon cancer cell proliferation and survival, since its downregulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumors, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Additionally, we found that functional categories, significantly affected by DDHD1 silencing, were specifically related to cancer phenotype and for the first time associated to DDHD1 activity.
In conclusion, this study provides the first evidence confirming the role of DDHD1 in cancer, providing a possibility to define a new target to design more effective therapies for colon cancer patients.
我们之前的研究表明，柠檬衍生的纳米囊泡能够降低结肠癌细胞的活力，这种作用与细胞内磷脂酶 DDHD 结构域蛋白 1（DDHD1）的下调有关。虽然目前关于 DDHD1 在神经疾病中的作用的研究很少，但关于其在癌症中的作用尚无信息。本研究探讨了 DDHD1 在结肠癌中的作用。
将 DDHD1 siRNA 和过表达载体转染到结直肠癌细胞和正常细胞中，以下调或上调 DDHD1 的表达。进行体外和体内实验，以研究 DDHD1 在结直肠癌细胞生长中的功能作用。使用 SWATH-MS 进行定量蛋白质组学分析，以确定 DDHD1 沉默在结直肠癌细胞中诱导的分子作用。
结果表明，DDHD1 支持结肠癌细胞的增殖和存活，因为其下调降低了体外结肠癌细胞的活力并增加了细胞凋亡率，而对正常细胞没有影响。相反，体内研究表明，源自 DDHD1 过表达细胞的异种移植肿瘤与对照动物相比具有更高的增殖率。此外，我们发现，功能类别受 DDHD1 沉默的显著影响，这些类别与癌症表型特异性相关，并且首次与 DDHD1 活性相关。
总之，本研究首次提供了 DDHD1 在癌症中的作用的证据，为设计针对结肠癌患者的更有效的治疗方法提供了新的靶标。
