miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1
miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1
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miR-138-1通过靶向PDK1调控黄曲霉毒素B1诱导的BEAS-2B细胞恶性转化
DOI：
10.1007/s00204-015-1551-4
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
王守林
中科院分区：
文献类型：
--
作者：
王超;孙真真;高卫民;王守林
环境致癌物诱发肺癌及其潜在机制引起了广泛关注。目前，microRNAs （miRNAs）已经被认为是癌症发展的关键参与者，其中miRNA的引导链而不是其客运链（miRNA*）已被广泛报道。我们之前的研究表明，0.1 nM AFB1处理50代可诱导稳定表达CYP2A13的永生化人支气管上皮细胞（P50 B-2A13细胞）的恶性转化。然而，mirna在这一致癌过程中的作用尚不清楚。本研究首先通过miRNA芯片鉴定P50 B-2A13细胞中36个上调miRNA和27个下调miRNA，通过RT-qPCR和中试实验选择miR-138-1*作为候选miRNA。功能研究显示miR-138-1*能够抑制P50 B-2A13细胞的增殖、集落形成、迁移和侵袭。此外，靶分析和双荧光素酶报告基因检测发现，miR-138-1*必然与3-磷酸肌醇依赖性蛋白激酶-1 （PDK1）的3 ' -UTR配对，并降低了荧光素酶活性。miR-138-1*可降低PI3K/PDK/Akt通路中PDK1及其下游蛋白的表达，反之则不能，提示miR-138-1*可能通过靶向PDK1影响afb1诱导的恶性转化。正如预测的那样，PDK1的干扰对P50 B-2A13细胞的增殖、集落形成、迁移和侵袭的影响与miR-138-1*相似。我们的研究表明，miR-138-1*通过靶向PDK1在afb诱导的B-2A13细胞恶性转化中发挥关键作用。尽管如此，该研究为miRNA*在致癌过程中的作用提供了新的见解，特别是空气中致癌物质诱发的肺癌。
Environmental carcinogens-induced lung cancer and potential mechanisms have attracted widespread attention. Currently, microRNAs (miRNAs) have been recognized as key players in development of cancer, among which guide strand of miRNA has been well documented rather than its passenger strand (miRNA*). Our previous study showed that treatment of 0.1 nM AFB1 for 50 passages could induce malignant transformation of immortalized human bronchial epithelial cells stably expressing CYP2A13 (P50 B-2A13 cells). However, the role of miRNAs in this carcinogenic proceeding is still unclear. In present study, 36 upregulated and 27 downregulated miRNAs in P50 B-2A13 cells were first identified by miRNA microarray, and miR-138-1* was selected as a candidate miRNA by RT-qPCR and pilot experiments. Functional studies revealed that miR-138-1* could inhibit proliferation, colony formation, migration and invasion of P50 B-2A13 cells. Further, target analysis and dual-luciferase reporter gene assay identified that miR-138-1*was consequentially paired with 3′-UTR of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and decreased the luciferase activity. miR-138-1* could decrease the expressions of PDK1 and its downstream proteins in PI3K/PDK/Akt pathway but not vice versa, indicating that miR-138-1* might affect AFB1-induced malignant transformation through targeting PDK1. As predicted, interference of PDK1 showed the similar effects to miR-138-1* in the proliferation, colony formation, migration and invasion of P50 B-2A13 cells. Our study demonstrated that miR-138-1* played a critical role in AFB-induced malignant transformation of B-2A13 cells by targeting PDK1. Still, the study provides a novel insight into the roles of miRNA* during carcinogenesis, particularly airborne carcinogens-induced lung cancer.
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DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
理解 microRNA 和环境因素的相互作用及其与人类疾病的关系
影响因子：
4.6
作者：
Qiu, Chengxiang;Chen, Geng;Cui, Qinghua
通讯作者：
Cui, Qinghua
影响因子：
3.8
作者：
Kensler, Thomas W.;Roebuck, Bill D.;Groopman, John D.
通讯作者：
Groopman, John D.
影响因子：
6.4
作者：
Yeh, Yu-Ming;Chuang, Chi-Mu;Wang, Lu-Hai
通讯作者：
Wang, Lu-Hai
影响因子：
4.8
作者：
Chang, Kuo-Wei;Kao, Shou-Yen;Lin, Shu-Chun
通讯作者：
Lin, Shu-Chun