Wang Min, Ge Xin, Zheng Jitai, Li Dongmei, Liu Xue, Wang Lin, Jiang Chengfei, Shi Zhumei, Qin Lianju, Liu Jiayin, Yang Hushan, Liu Ling-Zhi, He Jun, Zhen Linlin, Jiang Bing-Hua
State Key Laboratory of Reproductive Medicine, Department of Pathology, and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing, Jiangsu, China.
Ninggao Personalized Medicine and Technology Innovation Center, Nanjing, Jiangsu, China.
Oncotarget. 2016 Apr 5;7(14):17805-14. doi: 10.18632/oncotarget.7525.
High levels of arsenic in drinking water, soil, and air are associated with the higher incidences of several kinds of cancers worldwide, but the mechanism is yet to be fully discovered. Recently, a number of evidences show that dysregulation of microRNAs (miRNAs) induces carcinogenesis. In this study, we found miR-222 was upregulated in arsenic-transformed human lung epithelial BEAS-2B cells (As-T cells). Anti-miR-222 inhibitor treatment decreased cell proliferation, migration, tube formation, and induced apoptosis. In addition, anti-miR-222 inhibitor expression decreased tumor growth in vivo. We also found that inhibition of miR-222 induced the expression of its direct targets ARID1A and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and activated apoptosis of As-T cells in part through ARID1A downregulation. These results indicate that miR-222 plays an important role in arsenic-induced tumor growth.
全球范围内，饮用水、土壤和空气中的高砷含量与多种癌症的较高发病率相关，但其中的机制尚未完全明确。最近，大量证据表明，微小RNA（miRNA）失调会诱发癌症。在本研究中，我们发现miR-222在砷转化的人肺上皮BEAS-2B细胞（As-T细胞）中表达上调。抗miR-222抑制剂处理可降低细胞增殖、迁移、成管能力，并诱导细胞凋亡。此外，抗miR-222抑制剂表达可降低体内肿瘤生长。我们还发现，抑制miR-222可诱导其直接靶点AT丰富结合域蛋白1A（ARID1A）和第10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）的表达，并部分通过下调ARID1A激活As-T细胞的凋亡。这些结果表明，miR-222在砷诱导的肿瘤生长中起重要作用。
