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Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone

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Abstract

Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.

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Reference

  • Avallone B, Agnisola C, Cerciello R, Panzuto R, Simoniello P, Creti P, et al. Structural and functional changes in the zebrafish (Danio rerio) skeletal muscle after cadmium exposure. Cell Biol Toxicol. 2015;31:273–83.

    Article  CAS  PubMed  Google Scholar 

  • Bao L, Zhang Y, Wang J, Wang H, Dong N, Su X, et al. Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer. Cell Biol Toxicol. 2016;32:419–35.

    Article  CAS  PubMed  Google Scholar 

  • Bhargava M, Higgins L, Wendt CH, Ingbar DH. Application of clinical proteomics in acute respiratory distress syndrome. Clinical and translational medicine. 2014;3:34.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chauhan V, Breznan D, Thomson E, Karthikeyan S, Vincent R. Effects of ambient air particles on the endothelin system in human pulmonary epithelial cells (A549). Cell Biol Toxicol. 2005;21:191–205.

    Article  CAS  PubMed  Google Scholar 

  • Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009;15:5323–37.

    Article  Google Scholar 

  • Chen H, Song Z, Qian M, Bai C, Wang X. Selection of disease-specific biomarkers by integrating inflammatory mediators with clinical informatics in AECOPD patients: a preliminary study. J Cell Mol Med. 2012a;16:1286–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Wang Y, Bai C, Wang X. Alterations of plasma inflammatory biomarkers in the healthy and chronic obstructive pulmonary disease patients with or without acute exacerbation. J Proteome. 2012b;75:2835–43.

    Article  CAS  Google Scholar 

  • Chen Y, Watson AM, Williamson CD, Rahimi M, Liang C, Colberg-Poley AM, et al. Glucocorticoid receptor and histone deacetylase-2 mediate dexamethasone-induced repression of MUC5AC gene expression. Am J Respir Cell Mol Biol. 2012c;47:637–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng YS, Rees T, Wright J. A review of research on salivary biomarkers for oral cancer detection. Clinical and translational medicine. 2014;3:3.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chrysis D, Zaman F, Chagin AS, Takigawa M, Savendahl L. Dexamethasone induces apoptosis in proliferative chondrocytes through activation of caspases and suppression of the Akt-phosphatidylinositol 3′-kinase signaling pathway. Endocrinology. 2005;146:1391–7.

    Article  CAS  PubMed  Google Scholar 

  • Hesketh PJ, Sanz-Altamira P. Aprepitant, dexamethasone, and palonosetron in the prevention of doxorubicin/cyclophosphamide-induced nausea and vomiting. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 2012;20:653–6.

    Article  Google Scholar 

  • Hu X, Gao JH, Liao YJ, Tang SJ, Lu F. Dexamethasone alters epithelium proliferation and survival and suppresses Wnt/beta-catenin signaling in developing cleft palate. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2013;56:67–74.

    Article  CAS  Google Scholar 

  • Khodarev NN, Pitroda SP, Beckett MA, MacDermed DM, Huang L, Kufe DW, et al. MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer. Cancer Res. 2009;69:2833–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koga T, Kuwahara I, Lillehoj EP, Lu W, Miyata T, Isohama Y, et al. TNF-alpha induces MUC1 gene transcription in lung epithelial cells: its signaling pathway and biological implication. American journal of physiology Lung cellular and molecular physiology. 2007;293:L693–701.

    Article  CAS  PubMed  Google Scholar 

  • Lappi-Blanco E, Makinen JM, Lehtonen S, Karvonen H, Sormunen R, Laitakari K, et al. Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37:13811–20.

    Article  CAS  Google Scholar 

  • Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E, et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of oncology: official journal of the European Society for Medical Oncology. 2012;23(Suppl 7):vii56–64.

    Article  Google Scholar 

  • Price LC, Shao D, Meng C, Perros F, Garfield BE, Zhu J, et al. Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells. Respir Res. 2015;16:114.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi L, Wang L, Hou J, Zhu B, Min Z, Zhang M, et al. Targeting roles of inflammatory microenvironment in lung cancer and metastasis. Cancer Metastasis Rev. 2015;34:319–31.

    Article  CAS  PubMed  Google Scholar 

  • Shi L, Dong N, Fang X, Wang X. Regulatory mechanisms of TGF-beta1-induced fibrogenesis of human alveolar epithelial cells. J Cell Mol Med. 2016;20:2183–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Situ D, Wang J, Ma Y, Zhu Z, Hu Y, Long H, et al. Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer. Med Oncol. 2011;28(Suppl 1):S596–604.

    Article  PubMed  Google Scholar 

  • Wang X, Zhang Y, Nilsson CL, Berven FS, Andren PE, Carlsohn E, et al. Association of chromosome 19 to lung cancer genotypes and phenotypes. Cancer Metastasis Rev. 2015a;34:217–26.

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Zhang Y, Wan H, Dong N, Bao L, Sun X, et al. Global analyses of subtype- or stage-specific genes on chromosome 7 in patients with lung cancer. Cancer Metastasis Rev. 2015b;34:333–45.

    Article  PubMed  Google Scholar 

  • Wang DC, Shi L, Zhu Z, Gao D, Zhang Y. Genomic mechanisms of transformation from chronic obstructive pulmonary disease to lung cancer. Seminars in cancer biology. 2016a.

  • Wang LJ, Li J, Hao FR, Yuan Y, Li JY, Lu W, et al. Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen. Acta Pharmacol Sin. 2016b;37:845–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M, Wang DC, Wang X, Zhang Y. Correlation between mucin biology and tumor heterogeneity in lung cancer. Seminars in cell & developmental biology. 2016.

  • Yin L, Fang F, Song X, Wang Y, Huang G, Su J, et al. The pro-adhesive and pro-survival effects of glucocorticoid in human ovarian cancer cells. J Mol Endocrinol. 2016;57:61–72.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Wang H, Wang J, Bao L, Wang L, Huo J, et al. Global analysis of chromosome 1 genes among patients with lung adenocarcinoma, squamous carcinoma, large-cell carcinoma, small-cell carcinoma, or non-cancer. Cancer Metastasis Rev. 2015;34:249–64.

    Article  PubMed  Google Scholar 

  • Zhang Y, Wang DC, Shi L, Zhu B, Min Z, Jin J. Genome analyses identify the genetic modification of lung cancer subtypes. Seminars in cancer biology. 2016.

  • Zhu Y, Wang W, Wang X. Roles of transcriptional factor 7 in production of inflammatory factors for lung diseases. J Transl Med. 2015;13:273.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work was supported by Shanghai Leading Academic Discipline Project (B115), Zhongshan Distinguished Professor Grant (XDW), The National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81400035, 81570075, 81500058, 81500025), The Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600), Zhejiang Provincial Natural Science Foundation (Z15H010002), and Zhejiang Provincial Science Technology Department Foundation (WKJ-ZJ-1526).

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Correspondence to Xiangdong Wang.

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All experimental procedures were approved by the Zhongshan Hospital Research Ethics Committee, Fudan University, China.

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Xu, M., Wang, X. Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone. Cell Biol Toxicol 33, 361–371 (2017). https://doi.org/10.1007/s10565-017-9393-x

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  • DOI: https://doi.org/10.1007/s10565-017-9393-x

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