Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells

作者: Yiting Tang , Yayun Cui , Zengpeng Li , Zhuqing Jiao , Yong Zhang

DOI: 10.1186/S13046-016-0285-3

关键词: A549 cellPI3K/AKT/mTOR pathwayLung cancerRadiation therapyCancer researchRadioresistanceCancerMedicineExosomeImmunologyCell cycle

摘要: Lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly countries. Radiotherapy plays a critical role curative management of inoperable non-small cell lung (NSCLC) is also used as post-surgical treatment patients. Radioresistance an important factor that limits efficacy radiotherapy for NSCLC Increasing evidence suggests microRNAs (miRNAs) possess diverse cellular regulatory roles radiation responses. In this study, we miRNA microarray technology to identify serum miRNAs were differentially expressed before after We further examined biological function miR-208a on viability, apoptotic death cycle distribution human cells explored probable mechanism. Nine miRNAs, including miR-29b-3p, miR-200a-3p, miR-126-3p significantly down-regulated, whereas was only up-regulated patients (P < 0.05). The expression could be induced by X-ray irradiation cells. Forced promoted proliferation radioresistance via targeting p21 with corresponding activation AKT/mTOR pathway cells, down-regulation resulted opposite effects. addition, increased percentage undergoing apoptosis inhibited G1 phase arrest Moreover, from exosome fraction shuttle A549 time-dependent manner, which likely contribute subsequent present study provides can affect radiosensitivity transported exosomes. Thus, may serve potential therapeutic target

参考文章(49)
J Ratajczak, M Wysoczynski, F Hayek, A Janowska-Wieczorek, M Z Ratajczak, Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia. ,vol. 20, pp. 1487- 1495 ,(2006) , 10.1038/SJ.LEU.2404296
Joe Y Chang, Suresh Senan, Marinus A Paul, Reza J Mehran, Alexander V Louie, Peter Balter, Harry JM Groen, Stephen E McRae, Joachim Widder, Lei Feng, Ben EEM van den Borne, Mark F Munsell, Coen Hurkmans, Donald A Berry, Erik van Werkhoven, John J Kresl, Anne-Marie Dingemans, Omar Dawood, Cornelis JA Haasbeek, Larry S Carpenter, Katrien De Jaeger, Ritsuko Komaki, Ben J Slotman, Egbert F Smit, Jack A Roth, None, Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials Lancet Oncology. ,vol. 16, pp. 630- 637 ,(2015) , 10.1016/S1470-2045(15)70168-3
Olivier Morel, Florence Toti, B??n??dicte Hugel, Jean-Marie Freyssinet, Cellular microparticles: a disseminated storage pool of bioactive vascular effectors Current Opinion in Hematology. ,vol. 11, pp. 156- 164 ,(2004) , 10.1097/01.MOH.0000131441.10020.87
Ahmedin Jemal, Freddie Bray, Melissa M. Center, Jacques Ferlay, Elizabeth Ward, David Forman, Global cancer statistics CA: A Cancer Journal for Clinicians. ,vol. 61, pp. 69- 90 ,(1999) , 10.3322/CAAC.20107
Junichi Takamizawa, Hiroyuki Konishi, Kiyoshi Yanagisawa, Shuta Tomida, Hirotaka Osada, Hideki Endoh, Tomoko Harano, Yasushi Yatabe, Masato Nagino, Yuji Nimura, Tetsuya Mitsudomi, Takashi Takahashi, Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival Cancer Research. ,vol. 64, pp. 3753- 3756 ,(2004) , 10.1158/0008-5472.CAN-04-0637
Ruolin Zhao, Meijuan Chen, Zequn Jiang, Fengming Zhao, Beili Xi, Xu Zhang, Haian Fu, Kunfu Zhou, Platycodin-D Induced Autophagy in Non-Small Cell Lung Cancer Cells via PI3K/Akt/mTOR and MAPK Signaling Pathways. Journal of Cancer. ,vol. 6, pp. 623- 631 ,(2015) , 10.7150/JCA.11291
Cesare Gridelli, Paolo Maione, Antonio Rossi, The Potential Role of mTOR Inhibitors in Non-Small Cell Lung Cancer Oncologist. ,vol. 13, pp. 139- 147 ,(2008) , 10.1634/THEONCOLOGIST.2007-0171
Douglas Hanahan, Robert A. Weinberg, Hallmarks of cancer: the next generation. Cell. ,vol. 144, pp. 646- 674 ,(2011) , 10.1016/J.CELL.2011.02.013
C. J. Sherr, J. M. Roberts, CDK inhibitors: positive and negative regulators of G1-phase progression Genes & Development. ,vol. 13, pp. 1501- 1512 ,(1999) , 10.1101/GAD.13.12.1501
Frederik H. Igney, Peter H. Krammer, Death and anti-death: tumour resistance to apoptosis Nature Reviews Cancer. ,vol. 2, pp. 277- 288 ,(2002) , 10.1038/NRC776