Cao Hongwen, Feng Yigeng, Chen Lei
Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, Shanghai, China.
Basic Clin Pharmacol Toxicol. 2017 Mar;120(3):256-263. doi: 10.1111/bcpt.12687. Epub 2016 Dec 28.
As the main component of realgar, arsenic sulphide (As S ) contains antitumour activity by repressing cancer cell proliferation and migration in many tumours. However, the detailed mechanism of these processes is not clear yet. MicroRNAs (miRNAs) can function as tumour suppressor or oncogene based on their target mRNAs in different tumour tissues. Here, we found that As S could repress the overexpression of microRNA-372 (miR-372) in two prostate cancer cell lines and its overexpression promoted cell proliferation and migration. Large tumour suppressor kinase 2 (LATS2) was confirmed as a direct target of miR-372 using luciferase assays in these two prostate cancer cell lines. Down-regulation of LATS2 could promote prostate cancer cell proliferation and migration just as overexpression of miR-372 did and overexpression of LATS2 could reverse this effect of miR-372. The antitumour activity of As S and the oncogenic function of miR-372 were further confirmed using a mouse xenograft model. Altogether, our data showed evidence that repressing the overexpression of miR-372 by As S could inhibit prostate cancer cell proliferation and migration by targeting LATS2. Therefore, miR-372 may be a possible biomarker for the prediction of prostate cancer and As S may have potential therapeutic function for prostate cancer.
作为雄黄的主要成分，硫化砷（As₂S₂）在许多肿瘤中通过抑制癌细胞增殖和迁移而具有抗肿瘤活性。然而，这些过程的详细机制尚不清楚。微小RNA（miRNA）可根据其在不同肿瘤组织中的靶mRNA发挥肿瘤抑制因子或癌基因的作用。在此，我们发现As₂S₂可抑制两种前列腺癌细胞系中微小RNA-372（miR-372）的过表达，且miR-372的过表达促进细胞增殖和迁移。在这两种前列腺癌细胞系中使用荧光素酶测定法证实大肿瘤抑制激酶2（LATS2）是miR-372的直接靶标。LATS2的下调可像miR-372过表达一样促进前列腺癌细胞增殖和迁移，而LATS2的过表达可逆转miR-372的这种作用。使用小鼠异种移植模型进一步证实了As₂S₂的抗肿瘤活性和miR-372的致癌功能。总之，我们的数据表明，As₂S₂通过靶向LATS2抑制miR-372的过表达可抑制前列腺癌细胞增殖和迁移。因此，miR-372可能是预测前列腺癌的一种潜在生物标志物，而As₂S₂可能对前列腺癌具有潜在治疗作用。
