Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma.
Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy.
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, China.
Shuang
S
Wei
Department of Surgery, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan 430030, China.
Zun-Yi
ZY
Zhang
Department of Surgery, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan 430030, China.
Sheng-Ling
SL
Fu
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, China.
Jun-Gang
JG
Xie
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, China.
Xian-Sheng
XS
Liu
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, China.
Yong-Jian
YJ
Xu
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, China.
Jian-Ping
JP
Zhao
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, China.
Wei-Ning
WN
Xiong
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000072200:Ku Autoantigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
C000623205:MIRN623 microRNA, human; D035683:MicroRNAs; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000072200:Ku Autoantigen
Cancer Res. 2006 Nov 15;66(22):10902-10
17108127
Amino Acids. 2008 Feb;34(2):195-202
17031478
Cancer Metastasis Rev. 2006 Mar;25(1):9-34
16680569
Respir Med. 2010 Dec;104(12):1767-74
20833010
Cell. 2011 Oct 14;147(2):275-92
22000009
Oncotarget. 2015 Jan 30;6(3):1462-77
25596743
Nature. 2007 Oct 11;449(7163):682-8
17898713
Mol Med Rep. 2015 Apr;11(4):3108-14
25483817
Cell Death Differ. 2014 Jul;21(7):1150-9
24658401
Nature. 2004 Sep 16;431(7006):350-5
15372042
Oncogene. 2001 Feb 8;20(6):739-47
11314007
Mol Med Rep. 2015 May;11(5):3647-51
25544258
Adv Med Sci. 2013;58(1):73-82
23640949
J Exp Clin Cancer Res. 2012 Nov 27;31:99
23181744
Nature. 2008 Sep 4;455(7209):58-63
18668040
Cell. 2006 Nov 17;127(4):679-95
17110329
BMC Complement Altern Med. 2013 Oct 20;13:271
24138815
Nat Cell Biol. 2010 Mar;12 (3):247-56
20173740
Histol Histopathol. 2008 Jun;23(6):693-700
18366007
Cell. 2004 Jan 23;116(2):281-97
14744438
CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
22237781
Oncotarget. 2015 Apr 10;6(10 ):8046-61
25797267
Cell. 2009 Jun 12;137(6):1032-46
19524507
Cancer Lett. 2009 Jul 8;279(2):155-62
19251361
DNA Cell Biol. 2007 May;26(5):311-20
17504027
Cell Biol Int. 2001;25(5):411-20
11401328
Nat Commun. 2013;4:1877
23695671
J Biol Chem. 2006 Nov 17;281(46):34833-47
16984917
Mol Nutr Food Res. 2009 Mar;53(3):407-16
19072741
Ann N Y Acad Sci. 2010 Apr;1194:60-71
20536451
Int J Cancer. 2010 Dec 15;127(12):2893-917
21351269
Carcinogenesis. 2012 Mar;33(3):538-47
22226916
J Agric Food Chem. 2011 Aug 24;59(16):9032-8
21770460
Nat Rev Cancer. 2006 Jun;6(6):449-58
16723991
Am J Clin Oncol. 2003 Aug;26(4):e80-5
12902903
Am J Pathol. 2013 Mar;182(3):954-64
23306155
Cancer Res. 1995 Mar 15;55(6):1235-8
7882315
Food Chem Toxicol. 2009 Aug;47(8):1985-95
19457446
Biochim Biophys Acta. 2006 Apr;1765(2):223-34
16480833
Nutr Cancer. 2012;64(2):255-66
22211962
Cancer Genet. 2015 Mar;208(3):76-84
25772251
Tumour Biol. 2014 Jul;35(7):6983-97
24744142