通过饮用水长期接触砷是一个全球性健康问题，影响超过 2 亿人。砷是 I 类人类致癌物，会导致染色体不稳定 (CIN)。砷暴露是继紫外线辐射之后导致皮肤癌的第二常见原因。相对于癌前角化过度，hsa-miR-186 在砷诱导的鳞状细胞癌中过度表达。 hsa-miR-186 的预测靶标包括细胞周期调节因子，包括有丝分裂进展的调节因子。有丝分裂进展的中断可能导致 CI​​N。因此，我们假设 hsa-miR-186 过表达通过诱导 CIN 促进砷暴露 HaCaT 细胞的恶性转化。用pEP-hsa-miR-186表达载体或空载体转染的HaCaT细胞的稳定克隆在嘌呤霉素选择下维持并暴露于0或100nM NaAsO2并培养29周。与未暴露的空载体转染克隆相比，过表达 hsa-miR-186 并暴露于 NaAsO2 的 HaCaT 克隆在第 29 周时以随机方式显示出 CIN 和锚定独立生长增加。这些结果表明克隆变异介导过表达 hsa-miR-186 的人角质形成细胞中砷诱导的癌发生。版权所有 © 2023。由 Elsevier Inc. 出版。

Chronic arsenic exposure through drinking water is a global health issue, affecting >200 million people. Arsenic is a group I human carcinogen and causes chromosomal instability (CIN). Arsenic exposure is the second most common cause of skin cancer after UV radiation. hsa-miR-186 is overexpressed in arsenic-induced squamous cell carcinoma relative to premalignant hyperkeratosis. Among predicted targets of hsa-miR-186 are cell cycle regulators including regulators of mitotic progression. Disruption of mitotic progression can contribute to CIN. Thus, we hypothesized that hsa-miR-186 overexpression contributes to malignant transformation of arsenic exposed HaCaT cells by induction of CIN. Stable clones of HaCaT cells transfected with pEP-hsa-miR-186 expression vector or empty vector were maintained under puromycin selection and exposed to 0 or 100 nM NaAsO2 and cultured for 29 weeks. HaCaT clones overexpressing hsa-miR-186 and exposed to NaAsO2 showed increased CIN and anchorage independent growth at 29 weeks in a stochastic manner, in contrast to unexposed empty vector transfected clones. These results suggest that clonal variability mediates arsenic-induced carcinogenesis in hsa-miR-186 overexpressing human keratinocytes.Copyright © 2023. Published by Elsevier Inc.