Issue
miR-675 promotes disease progression of non-small cell lung cancer via activating NF-κB signaling pathway
Corresponding Author(s) : Y. Feng
Cellular and Molecular Biology,
Vol. 63 No. 5: Issue 5
Abstract
Non-small cell lung cancer (NSCLC) is a major type of lung cancer significantly affected human life. Current studies have revealed potential role of miR-675 in the etiology of lung cancer. Therefore, in this study, we aimed to investigate the role of miR-675 in NSCLC cell line. We recruited 92 cases of NSCLC patients from July 2009 to February 2011 in the oncology department. Tumor and peripheral tissue was collected for miR-675 expression. NSCLC cell lines with either miR-675 over-expression or low-expression were established. Western blotting and immunofluorescence staining were used for detecting P65 and pP65 expression and translocation in the nuclei. MiR-675 expression was significantly higher in the lung cancer tissue than the peripheral normal tissue (P < 0.001). The gene expression of pP65 was also increased and decreased in cells with over-expression or low-expression of miR-675, respectively (both P < 0.05). Whereas the trend of P65 expression was on the opposite (both P < 0.05), indicating the NF-κB signaling pathway was activated when miR-675 was expressed and vice versa. Immunofluorescence staining showed that more pP65 expression was clustered in the nuclei in miR-675 over-expressed cells, which further demonstrated NF-κB signaling pathway activation. Increased miR-675 expression is associated with NSCLC progression through activation of NF-κB signaling pathway.
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- Hong QY, Wu GM, Qian GS, Hu CP, Zhou JY, Chen LA, et al. Prevention and management of lung cancer in China. Cancer. 2015;121:3080-8.
- Islami F, Torre LA, Jemal A. Global trends of lung cancer mortality and smoking prevalence. Transl Lung Cancer Res. 2015;4:327-38.
- Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics. Adv Exp Med Biol. 2016;893:1-19.
- Saintigny P, Burger JA. Recent advances in non-small cell lung cancer biology and clinical management. Discov Med. 2012;13:287-97.
- Califano R, Abidin A, Tariq NU, Economopoulou P, Metro G, Mountzios G. Beyond EGFR and ALK inhibition: unravelling and exploiting novel genetic alterations in advanced non small-cell lung cancer. Cancer Treat Rev. 2015;41:401-11.
- Ortholan C, Puissegur MP, Ilie M, Barbry P, Mari B, Hofman P. MicroRNAs and lung cancer: new oncogenes and tumor suppressors, new prognostic factors and potential therapeutic targets. Curr Med Chem. 2009;16:1047-61.
- Bueno MJ, Malumbres M. MicroRNAs and the cell cycle. Biochim Biophys Acta. 2011;1812:592-601.
- Su Z, Yang Z, Xu Y, Chen Y, Yu Q. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget. 2015;6:8474-90.
- Wang J, Zhao YC, Lu YD, Ma CP. Integrated bioinformatics analyses identify dysregulated miRNAs in lung cancer. Eur Rev Med Pharmacol Sci. 2014;18:2270-4.
- Del Prete A, Allavena P, Santoro G, Fumarulo R, Corsi MM, Mantovani A. Molecular pathways in cancer-related inflammation. Biochem Med (Zagreb). 2011;21:264-75.
- Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12:584-96.
- Karin M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex. Oncogene. 1999;18:6867-74.
- He D, Wang J, Zhang C, Shan B, Deng X, Li B, et al. Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer. Mol Cancer. 2015;14:73.
- Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ, et al. Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 2010;31:350-8.
- Zhuang M, Gao W, Xu J, Wang P, Shu Y. The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1. Biochem Biophys Res Commun. 2014;448:315-22.
- Liu C, Chen Z, Fang J, Xu A, Zhang W, Wang Z. H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation. Tumour Biol. 2016;37:263-70.
- Chen SJ, Huang SS, Chang NS. Role of WWOX and NF-κB in lung cancer progression. Transl Respir Med. 2013;1:15.
- Lee JI, Burckart GJ. Nuclear factor kappa B: important transcription factor and therapeutic target. J Clin Pharmacol. 1998;38:981-93.
References
Hong QY, Wu GM, Qian GS, Hu CP, Zhou JY, Chen LA, et al. Prevention and management of lung cancer in China. Cancer. 2015;121:3080-8.
Islami F, Torre LA, Jemal A. Global trends of lung cancer mortality and smoking prevalence. Transl Lung Cancer Res. 2015;4:327-38.
Torre LA, Siegel RL, Jemal A. Lung Cancer Statistics. Adv Exp Med Biol. 2016;893:1-19.
Saintigny P, Burger JA. Recent advances in non-small cell lung cancer biology and clinical management. Discov Med. 2012;13:287-97.
Califano R, Abidin A, Tariq NU, Economopoulou P, Metro G, Mountzios G. Beyond EGFR and ALK inhibition: unravelling and exploiting novel genetic alterations in advanced non small-cell lung cancer. Cancer Treat Rev. 2015;41:401-11.
Ortholan C, Puissegur MP, Ilie M, Barbry P, Mari B, Hofman P. MicroRNAs and lung cancer: new oncogenes and tumor suppressors, new prognostic factors and potential therapeutic targets. Curr Med Chem. 2009;16:1047-61.
Bueno MJ, Malumbres M. MicroRNAs and the cell cycle. Biochim Biophys Acta. 2011;1812:592-601.
Su Z, Yang Z, Xu Y, Chen Y, Yu Q. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget. 2015;6:8474-90.
Wang J, Zhao YC, Lu YD, Ma CP. Integrated bioinformatics analyses identify dysregulated miRNAs in lung cancer. Eur Rev Med Pharmacol Sci. 2014;18:2270-4.
Del Prete A, Allavena P, Santoro G, Fumarulo R, Corsi MM, Mantovani A. Molecular pathways in cancer-related inflammation. Biochem Med (Zagreb). 2011;21:264-75.
Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12:584-96.
Karin M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex. Oncogene. 1999;18:6867-74.
He D, Wang J, Zhang C, Shan B, Deng X, Li B, et al. Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer. Mol Cancer. 2015;14:73.
Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ, et al. Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 2010;31:350-8.
Zhuang M, Gao W, Xu J, Wang P, Shu Y. The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1. Biochem Biophys Res Commun. 2014;448:315-22.
Liu C, Chen Z, Fang J, Xu A, Zhang W, Wang Z. H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation. Tumour Biol. 2016;37:263-70.
Chen SJ, Huang SS, Chang NS. Role of WWOX and NF-κB in lung cancer progression. Transl Respir Med. 2013;1:15.
Lee JI, Burckart GJ. Nuclear factor kappa B: important transcription factor and therapeutic target. J Clin Pharmacol. 1998;38:981-93.