Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Biochem Biophys Res Commun. 2020 Apr 9;524(3):663-671. doi: 10.1016/j.bbrc.2020.01.020. Epub 2020 Feb 6.
Colorectal cancer (CRC) is known for being a great threat to human health due to its high incidence and mortality. ADAMTS8 that belongs to the zinc metalloproteinases family acts as a tumor suppressor and is silenced by CpG methylation in several carcinomas through previous studies, but its functions in CRC remain unknown. In this report, we analyzed its expression in CRC cell lines and primary CRC tumor tissues. The results showed that ADAMTS8 was significantly down-regulated in CRC cell lines and primary tumor tissues and its expression was restored in Lovo cell lines with treatment DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine and TSA. Over-expression of ADAMTS8 in HCT116 and HT-29 resulted in inhibited cell proliferation and induced apoptosis. We also observed that ADAMTS8 suppressed cell invasion and migration. In addition, ADAMTS8 induced cell cycle arrest in G2/M phase. Furthermore, we found that ADAMTS8 led to the decrease of BCL-XL, phospho-GSK3β, β-catenin and c-myc as well as increase of cleaved caspase-9, Bax and PARP. Our findings suggest that ADAMTS8 may be considered as a functional tumor suppressor gene in CRC and has the potential to be developed as a valuable biomarker.
结直肠癌（CRC）由于其高发病率和死亡率，是对人类健康的巨大威胁。ADAMTS8 属于锌金属蛋白酶家族，作为一种肿瘤抑制因子，通过之前的研究发现其在几种癌中被 CpG 甲基化沉默，但在 CRC 中的作用仍不清楚。在本报告中，我们分析了 ADAMTS8 在 CRC 细胞系和原发性 CRC 肿瘤组织中的表达。结果表明，ADAMTS8 在 CRC 细胞系和原发性肿瘤组织中显著下调，用 DNA 甲基转移酶抑制剂 5-氮杂-2′-脱氧胞苷和 TSA 处理 Lovo 细胞系后其表达得到恢复。ADAMTS8 在 HCT116 和 HT-29 中的过表达导致细胞增殖受到抑制并诱导细胞凋亡。我们还观察到 ADAMTS8 抑制细胞侵袭和迁移。此外，ADAMTS8 诱导细胞周期停滞在 G2/M 期。此外，我们发现 ADAMTS8 导致 BCL-XL、磷酸化-GSK3β、β-catenin 和 c-myc 减少，以及 cleaved caspase-9、Bax 和 PARP 增加。我们的研究结果表明，ADAMTS8 可能被认为是 CRC 中的功能性肿瘤抑制基因，并有可能作为有价值的生物标志物进行开发。
