Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer.
Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer.
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DOI：
10.1007/s00204-021-03084-2
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发表时间：
2021-07
影响因子：
6.1
通讯作者：
States JC
中科院分区：
文献类型：
--
作者：
Banerjee M;Ferragut Cardoso A;Al-Eryani L;Pan J;Kalbfleisch TS;Srivastava S;Rai SN;States JC
慢性砷暴露会导致皮肤癌，尽管其潜在的分子机制尚不清楚。 microRNA 和 mRNA 表达的改变可能在致癌过程中发挥关键作用。在经过充分验证的砷诱导皮肤鳞状细胞癌 (cSCC) HaCaT 细胞系模型中，研究了慢性亚砷酸钠 (As3+) 暴露后 3 个战略时间点的 miRNA 和 mRNA 全基因组差异表达的变化。将四份独立的 HaCaT 细胞培养物暴露于 0 或 100 nM As3+ 长达 28 周 (wk)。在整个暴露过程中监测细胞生长，并使用免疫印迹检查上皮间质转化（EMT）。通过 RNA-seq 在第 7、19 和 28 周生成差异表达的 miRNA 和 mRNA 谱，然后通过每个时间点的表达配对来鉴定差异表达 miRNA 的差异表达 mRNA 靶标。对每个时间点的总差异表达 mRNA 和 miRNA 靶向 mRNA 进行通路分析。 RNA-seq 预测通过所选靶蛋白的免疫印迹进行验证。虽然暴露于 As3+ 的细胞最初生长较慢，但到 19 周（转化起始）时，生长速度与未暴露的细胞相同，并且暴露的细胞随后比传代匹配的未暴露的细胞生长得更快。 As3+ 暴露的细胞在 28 周时经历了 EMT。通路分析表明，在每个时间点，致癌相关通路和网络以复杂的协调方式失调。免疫印迹数据很大程度上证实了内质网应激（ER 应激）途径中 RNA-seq 的预测。这项研究提供了砷诱导的人类角质形成细胞转化过程中发生变化的详细分子图谱。在线版本包含可在 10.1007/s00204-021-03084-2 获取的补充材料。
Chronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes. The online version contains supplementary material available at 10.1007/s00204-021-03084-2.
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影响因子：
10.4
作者：
Applebaum KM;Karagas MR;Hunter DJ;Catalano PJ;Byler SH;Morris S;Nelson HH
通讯作者：
Nelson HH
影响因子：
3.6
作者：
Chen QY;Costa M
通讯作者：
Costa M
DOI：
10.1038/s41568-020-00312-2
发表时间：
2021-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Chen X;Cubillos-Ruiz JR
通讯作者：
Cubillos-Ruiz JR
影响因子：
3.8
作者：
Davey, Jennifer C.;Bodwell, Jack E.;Hamilton, Joshua W.
通讯作者：
Hamilton, Joshua W.
影响因子：
--
作者：
Alan, Jamie K;Lundquist, Erik A
通讯作者：
Lundquist, Erik A