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miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

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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Abbreviations

CYP:

Cytochrome P450

CYP2A13:

Cytochrome P450 2A13

AFB1:

Aflatoxin B1

BEAS-2B:

Immortalized human bronchial epithelial cells

B-2A13:

BEAS-2B cells stably expressing CYP2A13

P50 B-2A13:

Passage 50 B-2A13 cells with malignant transformation induced by AFB1

miRNAs:

MicroRNAs

PDK1:

3-Phosphoinositide-dependent protein kinase-1

EMT:

Epithelial–mesenchymal transitions

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Acknowledgments

This work was supported by National Natural Science Foundation of China (81372956, 81172695), Natural Science Foundation of Jiangsu Universities (14KJA330002), 333 Advance Talents Projects of Jiangsu Province (BRA2014285), Six Talents Peak Project of Jiangsu Province (DG216D5047) and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), China.

Conflict of interest

The authors indicate no potential conflicts of interest.

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    Authors and Affiliations

    1. Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, People’s Republic of China

      Yun Wang, Zhan Zhang, Huanqiang Wang, Yudong Zhang, Minghui Ji, Hengsen Xu, Chao Wang, Zhenzhen Sun & Shou-Lin Wang

    2. State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, People’s Republic of China

      Yun Wang, Zhan Zhang, Chao Wang & Shou-Lin Wang

    3. Department of Preventive Medicine, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, 233030, People’s Republic of China

      Yun Wang

    4. Department of Environmental Toxicology, Institute of Environmental and Human Health, Texas Tech University, 1207 Gilbert Drive, Lubbock, TX, 79416, USA

      Weimin Gao

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    Yun Wang and Zhan Zhang have contributed equally to this work.

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    Wang, Y., Zhang, Z., Wang, H. et al. miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1. Arch Toxicol 90, 1239–1249 (2016). https://doi.org/10.1007/s00204-015-1551-4

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