MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4.
MicroRNAs (miRs) are involved in the development and progression of hepatocellular carcinoma (HCC), but the regulatory mechanism of miR-98 in HCC still remains unclear. Here we found that miR-98 was significantly downregulated in HCC tissues compared to matched adjacent normal tissues (ANTs). Low miR-98 expression was associated with tumor size, metastasis, portal vein tumor embolus, and poor overall survival. Ectopic expression of miR-98 decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. SALL4 was identified as a novel target of miR-98, and the protein expression of SALL4 was inhibited by miR-98 in HCC cells. Overexpression of SALL4 reversed the suppressive effects of miR-98 on the malignant phenotypes of HCC cells. Besides, SALL4, upregulated in HCC tissues compared to the matched ANTs, was inversely correlated to the miR-98 levels in HCC tissues. In addition, overexpression of miR-98 markedly suppressed the tumor growth as well as tumor-induced death in nude mice. In summary, miR-98 plays a suppressive role in the proliferation, migration, invasion and EMT of HCC cells, partly at least, via directly inhibition of SALL4. Therefore, the miR-98/SALL4 axis may become a promising therapeutic target for HCC.
Department of Hepatobillary Surgery, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Wuyuan
W
Zhou
Department of Urology Surgery, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Benkui
B
Zou
Clinical Laboratory, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Lisheng
L
Liu
Department of Hepatobillary Surgery, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Kai
K
Cui
Department of Hepatobillary Surgery, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Jie
J
Gao
Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Shuanghu
S
Yuan
Department of Intervention Therapy, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Ning
N
Cong
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014162:Transfection
C546084:MIRN98 microRNA, human; D035683:MicroRNAs; C472575:SALL4 protein, human; D014157:Transcription Factors
SALL4; hepatocellular carcinoma; microRNA-98; tumor suppressor
Oncogene. 2014 Jul 31;33(31):4069-76
24013226
Int J Clin Exp Pathol. 2015 Oct 01;8(10 ):12252-9
26722410
PLoS One. 2015 Apr 09;10(4):e0123522
25856466
Oncotarget. 2015 Dec 29;6(42):44758-80
26556872
Cold Spring Harb Symp Quant Biol. 2008;73:203-9
19022762
Oncol Rep. 2011 Oct;26(4):965-70
21725617
Cancer Lett. 2015 Feb 1;357(1):55-62
25444934
Oncol Rep. 2011 Jan;25(1):273-9
21109987
Exp Mol Med. 2014 Oct 03;46:e116
25277211
Onco Targets Ther. 2015 Sep 22;8:2689-97
26445551
Nature. 2004 Sep 16;431(7006):350-5
15372042
Springerplus. 2014 Dec 10;3:721
26034695
Oncogene. 2014 Nov 27;33(48):5491-500
24276240
J Clin Med. 2016 Jan 26;5(2):null
26821054
Med Oncol. 2014 Apr;31(4):922
24659265
BMC Cancer. 2014 Apr 21;14:274
24751144
Eur Rev Med Pharmacol Sci. 2015 Oct;19(19):3593-604
26502849
Carcinogenesis. 2010 May;31(5):766-76
19843643
Cancer Res. 2014 Dec 15;74(24):7161-7
25477334
CA Cancer J Clin. 2015 Mar;65(2):87-108
25651787
Cell. 2004 Jan 23;116(2):281-97
14744438
Mol Med Rep. 2009 Nov-Dec;2(6):963-70
21475928
Curr Biol. 2002 Feb 19;12(4):R138-40
11864587
Liver Cancer. 2014 May;3(2):71-84
24944998
J Immunol Res. 2014;2014:262385
24860834
Sci Rep. 2015 Apr 28;5:9995
25919570
Gastroenterology. 2007 Aug;133(2):647-58
17681183
J Clin Med. 2016 Jan 27;5(2):null
26828526
Cell Physiol Biochem. 2013;32(3):655-62
24029877
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29
25559415
Neoplasma. 2015 ;62(6):980-8
26458308
J Hepatol. 2014 Jan;60(1):127-34
24012616
Nat Rev Cancer. 2006 Nov;6(11):857-66
17060945
Mol Cell Biol. 2009 Apr;29(7):1944-58
19139273
Hepatobiliary Pancreat Dis Int. 2003 Nov;2(4):529-36
14627514
Oncogene. 2015 Jan 2;34(1):63-72
24336327
Carcinogenesis. 2010 Sep;31(9):1516-22
20525879
Mol Cancer Res. 2009 Aug;7(8):1234-43
19671678
World J Stem Cells. 2013 Oct 26;5(4):172-87
24179605
Oncotarget. 2012 Nov;3(11):1370-85
23211491
Cancer Res. 2009 Feb 1;69(3):1135-42
19155302
N Engl J Med. 2013 Jun 13;368(24):2266-76
23758232
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13556-61
18768788