High Expression of TLR2 in the serum of patients with tuberculosis and lung cancer, and can promote the progression of lung cancer

Ming Zhang; Yingying Zhou; Yanli Zhang; Ming Zhang; Yingying Zhou; Yanli Zhang

doi:10.3934/mbe.2020104

Mathematical Biosciences and Engineering

2020, Volume 17, Issue 3: 1959-1972. doi: 10.3934/mbe.2020104

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High Expression of TLR2 in the serum of patients with tuberculosis and lung cancer, and can promote the progression of lung cancer

1.
Department of Thoracic Surgery, Da Qing Long Nan Hospital, Daqing 163453, China
2.
Department of Respiratory Medicine, Daqing Oilfield General Hospital, Daqing 163000, China

Received: 30 May 2019 Accepted: 06 December 2019 Published: 20 December 2019

PurposeThe present paper investigated the expression of TLR2 in serum of patients with pulmonary tuberculosis and lung cancer, and verifiedthe effect of TLR2 on the biological characteristics of lung cancer cells.

MethodsThe common differentially expressed genes in tuberculosis and lung cancer samples were analyzed by edgeR. The intersection of genes was taken and the enrichment analysis and string interaction analysis were performed. The expression of TLR2, inflammatory factors IL6, IL17 and IL22 in serum of patients with pulmonary tuberculosis or lung cancer and lung cell were detected by ELISA. The mRNA and protein expression levels of TLR2, caspase-3, Bax and Bcl-2 were detected by qRT-PCR and Western blot. CCK-8, colony formation assay, transwell assay and flow cytometry were performed to detect the proliferation, invasion, migration and cells apoptosis of lung cancer cells.

ResultsBioinformatics analysis found that high expression of TLR2 is a core regulator in lung cancer and tuberculosis. TLR2 and inflammatory factors IL6, IL17, IL22 are highly expressed in the serum of patients with tuberculosis and lung cancer by ELISA.TLR2 is also highly expressed in lung cancer cells. Silencing TLR2 inhibited the growth, invasion and migration ability of cells, and the expression of IL6, IL17 and IL22. It also promoted the expression of caspase-3 and Baxwith the decreased expression of Bcl-2.

ConclusionTLR2 and inflammatory factors IL6, IL17 and IL22 were highly expressed in the serum of patients with pulmonary tuberculosis and lung cancer. Silencing TLR2 could inhibit the growth, invasion and migration ability of lung cancer cells, and promote apoptosis.
- lung cancer,
- tuberculosis,
- TLR2,
- inflammatory factor,
- proliferation and metastasis
Citation: Ming Zhang, Yingying Zhou, Yanli Zhang. High Expression of TLR2 in the serum of patients with tuberculosis and lung cancer, and can promote the progression of lung cancer[J]. Mathematical Biosciences and Engineering, 2020, 17(3): 1959-1972. doi: 10.3934/mbe.2020104

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Abstract

PurposeThe present paper investigated the expression of TLR2 in serum of patients with pulmonary tuberculosis and lung cancer, and verifiedthe effect of TLR2 on the biological characteristics of lung cancer cells.

MethodsThe common differentially expressed genes in tuberculosis and lung cancer samples were analyzed by edgeR. The intersection of genes was taken and the enrichment analysis and string interaction analysis were performed. The expression of TLR2, inflammatory factors IL6, IL17 and IL22 in serum of patients with pulmonary tuberculosis or lung cancer and lung cell were detected by ELISA. The mRNA and protein expression levels of TLR2, caspase-3, Bax and Bcl-2 were detected by qRT-PCR and Western blot. CCK-8, colony formation assay, transwell assay and flow cytometry were performed to detect the proliferation, invasion, migration and cells apoptosis of lung cancer cells.

ResultsBioinformatics analysis found that high expression of TLR2 is a core regulator in lung cancer and tuberculosis. TLR2 and inflammatory factors IL6, IL17, IL22 are highly expressed in the serum of patients with tuberculosis and lung cancer by ELISA.TLR2 is also highly expressed in lung cancer cells. Silencing TLR2 inhibited the growth, invasion and migration ability of cells, and the expression of IL6, IL17 and IL22. It also promoted the expression of caspase-3 and Baxwith the decreased expression of Bcl-2.

ConclusionTLR2 and inflammatory factors IL6, IL17 and IL22 were highly expressed in the serum of patients with pulmonary tuberculosis and lung cancer. Silencing TLR2 could inhibit the growth, invasion and migration ability of lung cancer cells, and promote apoptosis.

References

[1]	J. Didkowska, U. Wojciechowska, M. Manczuk, J. Lobaszewski, Lung cancer epidemiology: Contemporary and future challenges worldwide, Ann. Transl. Med., 4 (2016), 150.
[2]	J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, et al., Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012, Int. J. Cancer, 136 (2015), E359-E386.
[3]	S. L. Wood, M. Pernemalm, P. A. Crosbie, A. D. Whetton, Molecular histology of lung cancer: From targets to treatments, Cancer Treat. Rev., 41 (2015), 361-375.
[4]	W. Chen, R. Zheng, P. D. Baade, S. Zhang, H. Zeng, F. Bray, et al., Cancer statistics in China, 2015, CA Cancer J. Clin., 66 (2016), 115-132.
[5]	W. Chen, R. Zheng, H. Zeng, S. Zhang, J. He, Annual report on status of cancer in China, 2011, Chin. J. Cancer Res., 27 (2015), 2-12.
[6]	K. V. Korneev, K. N. Atretkhany, M. S. Drutskaya, S. I. Grivennikov, D. V. Kuprash, S. A. Nedospasov, TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis, Cytokine, 89 (2017), 127-135.
[7]	C. P. Liao, R. C. Booker, J. P. Brosseau, Z. Chen, J. Mo, E. Tchegnon, et al., Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis, J. Clin. Invest., 128 (2018), 2848-2861.
[8]	B. Benner, L. Scarberry, A. Stiff, M. C. Duggan, L. Good, G. Lapurga, et al., Evidence for interaction of the NLRP3 inflammasome and Bruton's tyrosine kinase in tumor-associated macrophages: Implications for myeloid cell production of interleukin-1beta, Oncoimmunology, 8 (2019), 1659704.
[9]	E. Giacomini, E. Iona, L. Ferroni, M. Miettinen, L. Fattorini, G. Orefici, et al., Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response, J. Immunol., 166 (2001), 7033-7041. doi: 10.4049/jimmunol.166.12.7033
[10]	S. J. S. Cameron, K. E. Lewis, M. Beckmann, G. G. Allison, R. Ghosal, P. D. Lewis, et al., The metabolomic detection of lung cancer biomarkers in sputum, Lung Cancer, 94 (2016), 88-95. doi: 10.1016/j.lungcan.2016.02.006
[11]	V. Y. F. Su, Y. F. Yen, S. W. Pan, P. H. Chuang, J. Y. Feng, K. T. Chou, et al., Latent tuberculosis infection and the risk of subsequent cancer, Medicine (Baltimore), 95 (2016), e2352.
[12]	H. Jia, L. Zhang, B. Wang, The value of combination analysis of tumor biomarkers for early differentiating diagnosis of lung cancer and pulmonary tuberculosis, Ann. Clin. Lab. Sci., 49 (2019), 645-649.
[13]	Y. Jiang, K. Ni, M. Fang, J. Li, The effects of serum hs-CRP on the incidence of lung cancer in male patients with pulmonary tuberculosis, Iran. J. Public Health, 48 (2019), 1265-1269.
[14]	J. Q. Chen, P. Szodoray, M. Zeher, Toll-Like Receptor Pathways in Autoimmune Diseases, Clin. Rev. Allergy Immunol., 50 (2016), 1-17.
[15]	S. A. Badi, S. Khatami, S. H. Irani, S. D. Siadat, Induction Effects of Bacteroides fragilis Derived Outer Membrane Vesicles on Toll Like Receptor 2, Toll Like Receptor 4 Genes Expression and Cytokines Concentration in Human Intestinal Epithelial Cells, Cell J., 21 (2018), 57-61.
[16]	J. Deng, Y. Q. Li, Y. Liu, Q. Li, Y. Hu, J. Q. Xu, et al., Exosomes derived from plasma of septic patients inhibit apoptosis of Tlymphocytes by down-regulating bad via hsa-miR-7-5p, Biochem. Biophys. Res. Commun., 513 (2019), 958-966.
[17]	E. Fathi, R. Farahzadi, B. Valipour, Z. Sanaat, Cytokines secreted from bone marrow derived mesenchymal stem cells promote apoptosis and change cell cycle distribution of K562 cell line as clinical agent in cell transplantation, Plos One, 14 (2019), e0215678.
[18]	B. Gur-Dedeoglu, O. Konu, B. Bozkurt, G. Ergul, S. Seckin, I. G. Yulug, Identification of endogenous reference genes for qRT-PCR analysis in normal matched breast tumor tissues, Oncol. Res., 17 (2009), 353-365.
[19]	M. D. Robinson, D. J. McCarthy, G. K. Smyth, edgeR: A Bioconductor package for differential expression analysis of digital gene expression data, Bioinformatics, 26 (2010), 139-140.
[20]	D. J. McCarthy, Y. Chen, G. K. Smyth, Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation, Nucleic Acids Res., 40 (2012), 4288-4297.
[21]	N. Xu, Y. P. Wu, H. B. Yin, X. Y. Xue, X. Gou, Molecular network-based identification of competing endogenous RNAs and mRNA signatures that predict survival in prostate cancer, J. Transl. Med., 16 (2018), 274.
[22]	S. Arora, S. Ahmad, R. Irshad, Y. Goyal, S. Rafat, N. Siddiqui, et al., TLRs in pulmonary diseases, Life Sci., 233 (2019), 116671.
[23]	X. Gu, Y. Gao, D. G. Mu, E. Q. Fu, MiR-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through TLR2/MyD88/NF-kappaB pathway by targeting TLR2, Exp. Cell Res., 354 (2017), 71-77.
[24]	S. Kim, H. Takahashi, W. Lin, P. Descargues, S. Grivennikov, Y. Kim, et al., Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis, Nature, 457 (2009), 102-106.
[25]	S. D. Gowing, S. C. Chow, J. J. Cools-Lartigue, C. B. Chen, S. Najmeh, H. Y. Jiang, et al., Gram-positive pneumonia augments non-small cell lung cancer metastasis via host toll-like receptor 2 activation, Int. J. Cancer, 141 (2017), 561-571.
[26]	S. I. Grivennikov, F. R. Greten, M. Karin, Immunity, inflammation, and cancer, Cell, 140 (2010), 883-899.
[27]	C. D. Palani, L. Ramanathapuram, A. Lam-Ubol, Z. B. Kurago, Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases (1/2), Oncotarget, 9 (2018), 6814-6829.
[28]	C. Molina-Romero, O. Arrieta, R. Hernandez-Pando, Tuberculosis and lung cancer, Salud Publica Mex., 61 (2019), 286-291.
[29]	D. Barh, S. Tiwari, R. N. Kumavath, P. Ghosh, V. Azevedo, Linking common non-coding RNAs of human lung cancer and M. tuberculosis, Bioinformation, 14 (2018), 337-345.

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