Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Department of Oncological Surgery, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Kunshan 215300, China.
Acta Biochim Biophys Sin (Shanghai). 2017 Oct 1;49(10):926-934. doi: 10.1093/abbs/gmx094.
SLC39A7 (zip7) is a zinc transporter that plays a key role in intestinal epithelial self-renewal. However, little is known about SLC39A7 in colorectal cancer. To assess the biological function of SLC39A7 in colorectal cancer, the expression of SLC39A7 in human colorectal tumors and five colorectal cancer cell lines were evaluated by Oncomine Cancer Microarray Database and western blot analysis. In addition, short hairpin RNAs specifically targeting SLC39A7 were transfected into HCT116 and SW1116 cells to knockdown SLC39A7 expression. Then, the effects of SLC39A7 knockdown on colorectal cancer cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide, colony-forming assay and flow cytometry. Our results showed that colorectal tumors have higher expression levels of SLC39A7 than normal colon tissues. Knockdown of SLC39A7 exhibited a significant decrease in cell viability and proliferation of colorectal cancer cells. It was also shown that knockdown of SLC39A7 interfered with cell cycle progression and induced G2/M cell cycle arrest, as well as boosted early and late apoptosis in colorectal cancer cells. Furthermore, downregulation of SLC39A7 promoted the cleavage of PARP and enhanced the expression of Bad, Caspase-9, and cleaved-Caspase-3, as well as suppressed Bcl-2 expression. In conclusion, our results suggest that SLC39A7 plays a crucial role in the proliferation and survival of colorectal cancer cells, which associates with colorectal tumorigenesis.
SLC39A7（zip7）是一种锌转运蛋白，在肠上皮细胞自我更新中发挥关键作用。然而，关于结直肠癌中的 SLC39A7 知之甚少。为了评估 SLC39A7 在结直肠癌中的生物学功能，通过 Oncomine Cancer Microarray Database 和 Western blot 分析评估了 SLC39A7 在人结直肠肿瘤和五株结直肠癌细胞系中的表达。此外，将特异性靶向 SLC39A7 的短发夹 RNA 转染到 HCT116 和 SW1116 细胞中以敲低 SLC39A7 的表达。然后，通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、集落形成测定和流式细胞术检测 SLC39A7 敲低对结直肠癌细胞的影响。我们的结果表明，结直肠肿瘤中的 SLC39A7 表达水平高于正常结肠组织。敲低 SLC39A7 可显著降低结直肠癌细胞的活力和增殖。此外，敲低 SLC39A7 干扰细胞周期进程并诱导 G2/M 细胞周期阻滞，并在结直肠癌细胞中诱导早期和晚期凋亡。此外，下调 SLC39A7 促进 PARP 的切割，并增强 Bad、Caspase-9 和 cleaved-Caspase-3 的表达，同时抑制 Bcl-2 的表达。总之，我们的结果表明 SLC39A7 在结直肠癌细胞的增殖和存活中发挥着重要作用，与结直肠肿瘤发生有关。
