J Cancer 2020; 11(5):1270-1276. doi:10.7150/jca.35453 This issue Cite

Research Paper

Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells

Maojun Zhou1*, Jinfeng Zhao2*, Qi Zhang3, Xin Jin2, Mingmei Liao2, Lihua Zhang2, Jiwei Wang2, Manyi Yang2✉

1. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
2. Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
3. Department of Hepatobiliary & Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, China.
*These authors contributed equally to this study.

Citation:
Zhou M, Zhao J, Zhang Q, Jin X, Liao M, Zhang L, Wang J, Yang M. Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells. J Cancer 2020; 11(5):1270-1276. doi:10.7150/jca.35453. https://www.jcancer.org/v11p1270.htm
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Abstract

Background: Nicotine contributes to development of human lung cancer and chemoresistance through activation of myeloid cell leukemia-1 (Mcl-1). Signal transducer and activator of transcription 3 (STAT3) generally participates in development and progression of human cancers. Therefore, we examined the STAT3 cascade in nicotine regulation of Mcl-1 transcription in human lung cancer cells.

Methods: The effects of nicotine on the expression of STAT3 and Mcl-1 were determined using western blot. The sub-cellular localization was tested using immunofluorescence. The activity of STAT3 promoter was checked using dual luciferase reporter assay.

Results: STAT3 was constitutively activated (i.e., tyrosine-phosphorylated, serine-phosphorylated and nuclear translocation), meanwhile the expression and transcriptional activity of Mcl-1 were up-regulated in lung cancer cells following treatment with nicotine. Transfection with siRNA targeting STAT3 or treatment with STAT3 inhibitor JSI-124 diminished Mcl-1 protein levels. Deleted mutagenesis of a putative STAT3 consensus binding sequence decreased Mcl-1 promoter activity and eliminated the increase of Mcl-1 promoter activity induced by nicotine. Abnormally, JAK (Jannus kinase) inhibitor AG490 can't induce the downregulation of Mcl-1 or inhibit the tyrosine-phosphorylation of STAT3. In addition, deactivated mutagenesis of STAT3 the tyrosine 705 site had no effect on the aggregation of STAT3 into nucleus induced by nicotine.

Conclusions: We have demonstrated that nicotine induces up-regulation of Mcl-1 through STAT3, which process may be independent on JAKs and not only dependent on the phosphorylation of Y705. Downregulation of Mcl-1 transcription by inhibiting STAT3 cascade may be a potential strategy for the treatment of this cancer.

Keywords: lung cancer, nicotine, Mcl-1, STAT3


Citation styles

APA
Zhou, M., Zhao, J., Zhang, Q., Jin, X., Liao, M., Zhang, L., Wang, J., Yang, M. (2020). Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells. Journal of Cancer, 11(5), 1270-1276. https://doi.org/10.7150/jca.35453.

ACS
Zhou, M.; Zhao, J.; Zhang, Q.; Jin, X.; Liao, M.; Zhang, L.; Wang, J.; Yang, M. Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells. J. Cancer 2020, 11 (5), 1270-1276. DOI: 10.7150/jca.35453.

NLM
Zhou M, Zhao J, Zhang Q, Jin X, Liao M, Zhang L, Wang J, Yang M. Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells. J Cancer 2020; 11(5):1270-1276. doi:10.7150/jca.35453. https://www.jcancer.org/v11p1270.htm

CSE
Zhou M, Zhao J, Zhang Q, Jin X, Liao M, Zhang L, Wang J, Yang M. 2020. Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells. J Cancer. 11(5):1270-1276.

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