Darshika Amarakoon, Wu-Joo Lee, Jing Peng, Seong-Ho Lee
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引用次数: 0
摘要
确定基因在癌症中的作用对于发现癌症治疗的潜在基因疗法至关重要。trans - loon -associated protein delta (TRAPδ),也被称为信号序列受体4 (SSR4),是TRAP/SSR复合物的一个组成单元,位于内质网中,在将新合成的蛋白质转运到内质网中起关键作用。然而,其在疾病发展中的生物学作用至今仍不清楚。这是首次在体外确定TRAPδ/SSR4在结直肠癌细胞中的作用的研究。在成功瞬时敲除TRAPδ/SSR4后,我们观察到在所测试的所有结直肠癌细胞系中细胞活力显著降低。HCT 116和SW480细胞株均在S期和G1期明显阻滞,而DLD-1细胞明显凋亡。此外,TRAPδ/SSR4稳定敲除的HCT 116和SW480细胞表现出显著降低的活力、不依赖于锚定的生长以及增加的S期和G1期阻滞。综上所述,我们认为TRAPδ/SSR4是人类结直肠癌细胞中的潜在致癌基因。
Identification of Translocon-associated Protein Delta as An Oncogene in Human Colorectal Cancer Cells.
Identifying the roles of genes in cancer is critical in discovering potential genetic therapies for cancer care. Translocon-associated protein delta (TRAPδ), also known as signal sequence receptor 4 (SSR4), is a constituent unit in the TRAP/SSR complex that resides in the endoplasmic reticulum and plays a key role in transporting newly synthesized proteins into the endoplasmic reticulumn. However, its biological role in disease development remains unknown to date. This is the first study to identify the role of TRAPδ/SSR4 in colorectal cancer cells in vitro. Upon successful transient knockdown of TRAPδ/SSR4, we observed significant reduction of cell viability in all colorectal cancer cell lines tested. Both HCT 116 and SW480 cell lines were significantly arrested at S and G1 phases, while DLD-1 cells were significantly apoptotic. Moreover, TRAPδ/SSR4 stable knockdown HCT 116 and SW480 cells showed significantly lower viability, anchorage-independent growth, and increased S and G1 phase arrests. Overall, we conclude TRAPδ/SSR4 is a potential oncogene in human colorectal cancer cells.