title: miR-135a/b modulate cisplatin resistance of human lung cancer cell line by targeting MCL1.
abstract: microRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of drug resistance in human lung cancer cell line. We found that miR-135a/b were downregulated while MCL1 was upregulated in A549/CDDP (cisplatin) cells, compared with the parental A549 cells. In vitro drug sensitivity assay demonstrated that overexpression of miR-135a/b sensitized A549/CDDP cells to cisplatin. The luciferase activity of MCL1 3'-untranslated region-based reporter constructed in A549/CDDP cells suggested that MCL1 was the direct target gene of miR-135a/b. Enforced miR-135a/b expression reduced MCL1 protein level and sensitized A549/CDDP cells to CDDP-induced apoptosis. Taken together, our findings first suggested that hsa-miR-135a/b could play a role in the development of CDDP resistance in lung cancer cell line at least in part by modulation of apoptosis via targeting MCL1.
authors: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors: Li
authors: L
authors: Zhou
authors: Tianzhu
authors: T
authors: Qiu
authors: Jing
authors: J
authors: Xu
authors: Tongshan
authors: T
authors: Wang
authors: Jian
authors: J
authors: Wang
authors: Xin
authors: X
authors: Zhou
authors: Zebo
authors: Z
authors: Huang
authors: Wei
authors: W
authors: Zhu
authors: Yongqian
authors: Y
authors: Shu
authors: Ping
authors: P
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C579095:MCL1 protein, human; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D002945:Cisplatin
references: Blood. 2011 Dec 22;118(26):6881-92
references: 22042699
references: Acta Biochim Biophys Sin (Shanghai). 2012 Mar;44(3):269-77
references: 22285729
references: J Mol Med (Berl). 2011 May;89(5):445-57
references: 21234533
references: Cell. 2002 Jan 25;108(2):153-64
references: 11832206
references: Nat Rev Drug Discov. 2006 Mar;5(3):219-34
references: 16518375
references: Blood. 2009 Oct 1;114(14):2945-51
references: 19666866
references: Drug Resist Updat. 2010 Jun;13(3):57-66
references: 20236855
references: Chin J Cancer. 2010 Mar;29(3):254-60
references: 20193106
references: Med Oncol. 2012 Dec;29(4):2527-34
references: 22101791
references: Expert Opin Investig Drugs. 2011 Oct;20(10):1397-411
references: 21851287
references: Acta Biochim Pol. 2005;52(3):609-27
references: 16175236
references: J Mol Neurosci. 2012 Jun;47(2):346-56
references: 22528454
references: Biochim Biophys Acta. 2009 Dec;1796(2):75-90
references: 19306912
references: Genes Cancer. 2011 Jul;2(7):720-7
references: 22207897
references: Pancreas. 2002 Nov;25(4):366-72
references: 12409831
references: Curr Med Chem. 2006;13(16):1859-76
references: 16842198
references: BMC Cancer. 2012 Mar 23;12:111
references: 22439757
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: Cold Spring Harb Symp Quant Biol. 2011;76:225-33
references: 22156303
references: Oncogene. 2012 Aug 23;31(34):3866-74
references: 22139076
references: Eur J Cancer. 2010 Jan;46(2):298-311
references: 19948396
references: Med Oncol. 2012 Mar;29(1):384-91
references: 21258880
references: FEBS Lett. 2012 May 7;586(9):1279-86
references: 22465665
references: Mol Carcinog. 2013 Jan;52(1):70-8
references: 22121083
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Int J Oncol. 1998 Apr;12(4):871-82
references: 9499449
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Br J Cancer. 1992 Nov;66(5):794-9
references: 1419622
references: Int J Biochem Cell Biol. 2010 Aug;42(8):1273-81
references: 20026422
references: Cell Stem Cell. 2007 Oct 11;1(4):389-402
references: 18371377
references: Drug Resist Updat. 2009 Aug-Oct;12(4-5):103-13
references: 19632887
references: Int J Cancer. 2008 Jul 15;123(2):372-379
references: 18449891
references: Cancer Treat Rev. 2007 Feb;33(1):9-23
references: 17084534