Cancer Cell International | |
Inhibition of miR-191 contributes to radiation-resistance of two lung cancer cell lines by altering autophagy activity | |
Shaoxiang Huang1  Zhenkuan Liu1  | |
[1] Department of Respiratory, Tianjin Fifth Central Hospital, 41 Zhejiang Road, Tianjin, China | |
关键词: Radiation-resistant; miR-191; Autophagy; Lung cancer; | |
Others : 1138563 DOI : 10.1186/s12935-015-0165-5 |
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received in 2014-11-28, accepted in 2015-01-20, 发布年份 2015 | |
【 摘 要 】
Background
Lung cancer is the leading cause of cancer-related morbidity and mortality all over the world. Surgery resection, radiotherapy, chemotherapy, immunotherapy and combined treatments have been discovered and well established for treatments. However, low survival rate of five years after clinical treatments mainly due to recurrence of stress-resistant cancer cells calls for better understanding and new ideas. Our project aimed to understand the forming process of stress resistant lung cancer cells after radiotherapy.
Methods
Two classic non-small cell lung cancer (NSCLC) cell lines A549 and H1299 initially were radiated with a 137Cs gamma-ray source with doses ranging from 0 to 12 Gy to generate radiation-resistant cancer cells. 8 Gy of radiation was regard as a standard dosage since it provides effective killing as well as good amount of survivals. The expression levels of autophagy-related proteins including Beclin-1, LC3-II and p62 were studied and measured by both western blot and quantitative real-time polymerase chain reaction (real-time RT-PCR).
Results
Increased Beclin-1, LC3-II and decreased p62 have been observed in radiation-resistant cells indicating elevated autophagy level. Decreased miR-191 in radiation-resistant cells performed by Taqman qRT-PCR also has been seen. Two binding sites between Beclin-1 and miR-191 suggest potential association between.
Conclusions
It is reasonable to speculate that inhibition of miR-191 expression in lung cancer cells would contribute to the establishment of radiation-resistant cells via mediating cellular autophagy. Therefore, miR-191 is a potential target for therapy in treating radiation-resistant lung cancer.
【 授权许可】
2015 Liu and Huang; licensee BioMed Central.
【 预 览 】
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【 参考文献 】
- [1]Investigators IELCAP, Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, et al.: Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006, 355(17):1763-71.
- [2]Miller YE: Pathogenesis of lung cancer: 100 year report. Am J Respir Cell Mol Biol 2005, 33(3):216-23.
- [3]Shields TW: Surgical therapy for carcinoma of the lung. Clin Chest Med 1993, 14(1):121-47.
- [4]Ettinger DS, Cox JD, Ginsberg RJ, Komaki R, Kris MG, Livingston RB, et al.: NCCN Non-Small-Cell Lung Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology 1996, 10(11 Suppl):81-111.
- [5]Lam WK: Management of non-small cell lung cancer according to staging–an update. Respirology 1998, 3(1):51-4.
- [6]Bach PB, Cramer LD, Warren JL, Begg CB: Racial differences in the treatment of early-stage lung cancer. N Engl J Med 1999, 341(16):1198-205.
- [7]Wu K-L, Jiang G-L, Qian H, Wang L-J, Yang H-J, Fu X-L, et al.: Three-dimensional conformal radiotherapy for locoregionally recurrent lung carcinoma after external beam irradiation: A prospective phase I-II clinical trial. Int J Radiat Oncol Biol Phys 2003, 57(5):1345-50.
- [8]Malissard L, Nguyen TD, Jung GM, Forcard JJ, Castelain B, Tuchais C, et al.: Localized adenocarcinoma of the lung: a retrospective study of 186 non-metastatic patients from the French Federation of Cancer Institutes–the Radiotherapy Cooperative Group. Int J Radiat Oncol Biol Phys 1991, 21(2):369-73.
- [9]Sugimura H, Nichols FC, Yang P, Allen MS, Cassivi SD, Deschamps C, et al.: Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Ann Thorac Surg 2007, 83(2):409-17. discussioin 417–408
- [10]Martini N, Bains MS, Burt ME, Zakowski MF, McCormack P, Rusch VW, et al.: Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 1995, 109(1):120-9.
- [11]Debnath J, Baehrecke EH, Kroemer G: Does autophagy contribute to cell death? Autophagy 2005, 1(2):66-74.
- [12]Lin N-Y, Beyer C, Gießl A, Kireva T, Scholtysek C, Uderhardt S, et al.: Autophagy regulates TNFα-mediated joint destruction in experimental arthritis. Ann Rheum Dis 2013, 72(5):761-8.
- [13]Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, et al.: Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 2005, 25(3):1025-40.
- [14]Yang ZJ, Chee CE, Huang S, Sinicrope FA: The role of autophagy in cancer: therapeutic implications. Mol Cancer Ther 2011, 10(9):1533-41.
- [15]Ambros V: The functions of animal microRNAs. Nature 2004, 431(7006):350-5.
- [16]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116(2):281-97.
- [17]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136(2):215-33.
- [18]Ambros V: MicroRNAs and developmental timing. Curr Opin Genet Dev 2011, 21(4):511-7.
- [19]Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120(1):15-20.
- [20]Lujambio A, Lowe SW: The microcosmos of cancer. Nature 2012, 482(7385):347-55.
- [21]Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 2009, 10(10):704-14.
- [22]Ma Q, Jiang Q, Pu Q, Zhang X, Yang W, Wang Y, et al.: MicroRNA-143 inhibits migration and invasion of human non-small-cell lung cancer and its relative mechanism. Int J Biol Sci 2013, 9(7):680-92.
- [23]Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, et al.: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005, 65(21):9628-32.
- [24]He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al.: A microRNA polycistron as a potential human oncogene. Nature 2005, 435(7043):828-33.
- [25]Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, et al.: Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 1998, 72(11):8586-96.
- [26]Yue Z, Jin S, Yang C, Levine AJ, Heintz N: Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 2003, 100(25):15077-82.
- [27]Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, et al.: Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol 2009, 11(4):468-76.
- [28]Wang SH, Martin SM, Harris PS, Knudson CM: Caspase inhibition blocks cell death and enhances mitophagy but fails to promote T-cell lymphoma. PLoS One 2011, 6(5):e19786.
- [29]Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, et al.: EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell 2013, 154(6):1269-84.
- [30]Jiang ZF, Shao LJ, Wang WM, Yan XB, Liu RY: Decreased expression of Beclin-1 and LC3 in human lung cancer. Mol Biol Rep 2012, 39(1):259-67.
- [31]Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, et al.: The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 2008, 13(4):343-54.
- [32]Ko A, Kanehisa A, Martins I, Senovilla L, Chargari C, Dugue D, et al.: Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling. Cell Death Differ 2014, 21(1):92-9.
- [33]Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al.: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006, 103(7):2257-61.
- [34]Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, et al.: Prognostic Values of microRNAs in Colorectal Cancer. Biomark Insights 2006, 2:113-21.
- [35]Nagpal N, Kulshreshtha R: miR-191: an emerging player in disease biology. Front Genet 2014, 5:99.
- [36]Patel RS, Jakymiw A, Yao B, Pauley BA, Carcamo WC, Katz J, et al.: High resolution of microRNA signatures in human whole saliva. Arch Oral Biol 2011, 56(12):1506-13.
- [37]Zou YM, Hu GY, Zhao XQ, Lu T, Zhu F, Yu SY, et al.: Hypoxia-induced autophagy contributes to radioresistance via c-Jun-mediated Beclin1 expression in lung cancer cells. J Huazhong Univ Sci Technolog Med Sci 2014, 34(5):761-7.