title: Overexpression of miR-22 reverses paclitaxel-induced chemoresistance through activation of PTEN signaling in p53-mutated colon cancer cells.
abstract: Chemoresistance is a key cause of treatment failure in colon cancer. MiR-22 is a tumor-suppressing microRNA. To explore whether miR-22 is an important player in the development of chemoresistance in colon cancer, we overexpressed miR-22 and subsequently tested its role in cell proliferation, apoptosis, survival, and associated signaling in p53-mutated HT-29 and HCT-15 cells, and p53 wild-type HCT-116 cells. We further investigated the role of miR-22 on cytotoxicity of paclitaxel in both the p53-mutated and p53 wild-type colon cancer cells. Results showed that HT-29 and HCT-15 cells were resistant to paclitaxel-induced cytotoxicity, which normally inhibits cell proliferation and survival, and induces apoptosis. Conversely, HCT-116 was relatively sensitive to the cytotoxicity of paclitaxel. Overexpression of miR-22 significantly decreased cell proliferation and survival, and induced cell apoptosis in the p53-mutated colon cancer cells, but played no role in the p53 wild-type cells. Importantly, miR-22 overexpression enhanced the cytotoxic role of paclitaxel in p53-mutated HT-29 and HCT-15 cells, but not in p53 wild-type HCT-116 cell. We further demonstrated that the tumor-suppressive role of miR-22 in p53-mutated colon cancer cells was mediated by upregulating PTEN expression, which negatively regulated Akt phosphorylation at Ser(473) and MTDH expression, and subsequently increased Bax and active caspase-3 levels. Our study is the first to identify the tumor-suppressive role of miR-22 and its associated signaling in the p53-mutated colon cancer cells and highlighted the chemosensitive role of miR-22.
authors: Hepatobiliary & Enteric Surgery Research Center, Central South University, Changsha 410008, China.
authors: Jian
authors: J
authors: Li
authors: Yangde
authors: Y
authors: Zhang
authors: Jingfeng
authors: J
authors: Zhao
authors: Fangren
authors: F
authors: Kong
authors: Yuxiang
authors: Y
authors: Chen
references: Oncogene. 2008 Sep 18;27(41):5443-53
references: 18794879
references: Oncol Rep. 2010 Oct;24(4):1029-34
references: 20811685
references: Nucleic Acids Res. 2006 Jul 19;34(12):3577-84
references: 16855294
references: Expert Opin Ther Targets. 2007 Dec;11(12):1611-21
references: 18020981
references: Oncogene. 2008 Feb 14;27(8):1114-21
references: 17704808
references: Cancer Cell. 2009 Jan 6;15(1):9-20
references: 19111877
references: PLoS One. 2010 May 27;5(5):e10859
references: 20523723
references: Genes Dev. 2006 Mar 1;20(5):515-24
references: 16510870
references: Adv Cancer Res. 2009;105:77-92
references: 19879424
references: Oncology (Williston Park). 2009 Feb;23(2):162-7
references: 19323297
references: Genet Eng (N Y). 2006;27:1-20
references: 16382868
references: Exp Cell Res. 2010 Nov 15;316(19):3197-206
references: 20736003
references: Biochem Biophys Res Commun. 2010 Apr 9;394(3):606-11
references: 20214878
references: J Formos Med Assoc. 2009 Mar;108(3):180-94
references: 19293033
references: Curr Top Med Chem. 2004;4(13):1347-56
references: 15379649
references: Mol Cancer Ther. 2007 Mar;6(3):898-906
references: 17363484
references: Eur J Pharm Sci. 2010 Sep 11;41(1):53-9
references: 20553861
references: Cancer Res. 2006 Feb 1;66(3):1509-16
references: 16452207
references: Carcinogenesis. 2007 Jul;28(7):1379-86
references: 17341655
references: Anticancer Agents Med Chem. 2009 Jun;9(5):543-9
references: 19519295
references: Jpn J Clin Oncol. 2011 Feb;41(2):287-90
references: 21068025
references: World J Gastroenterol. 2010 Feb 28;16(8):960-5
references: 20180234
references: Cancer Res. 2007 Jun 1;67(11):5248-57
references: 17545604
references: Clin Cancer Res. 2003 Mar;9(3):1155-60
references: 12631621
references: J Clin Oncol. 2005 Oct 20;23(30):7518-28
references: 16172461
references: Biochem Biophys Res Commun. 2006 Feb 24;340(4):1144-50
references: 16414349
references: Cancer Sci. 2005 Jul;96(7):394-402
references: 16053510
references: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17390-5
references: 17088530
references: Clin Cancer Res. 2009 Sep 15;15(18):5615-20
references: 19723648
references: Nat Rev Cancer. 2007 Aug;7(8):573-84
references: 17625587
references: Oncogene. 2010 Sep 2;29(35):4980-8
references: 20562918
references: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4507-11
references: 7753834