Long Noncoding RNA lncCAMTA1 Promotes Proliferation and Cancer Stem Cell-Like Properties of Liver Cancer by Inhibiting CAMTA1.
Hepatocellular carcinoma (HCC) is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC)-mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA) microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome. In vitro and in vivo functional experiments showed that overexpression of lncCAMTA1 promotes HCC cell proliferation, CSC-like properties, and tumorigenesis. Conversely, depletion of lncCAMTA1 inhibits HCC cell proliferation, CSC-like properties, and tumorigenesis. Mechanistically, we demonstrated that lncCAMTA1 physically associates with the calmodulin binding transcription activator 1 (CAMTA1) promoter, induces a repressive chromatin structure, and inhibits CAMTA1 transcription. Furthermore, CAMTA1 is required for the effects of lncCAMTA1 on HCC cell proliferation and CSC-like properties, and the expression of lncCAMTA1 and CAMTA1 is significantly negatively correlated in HCC tissues. Collectively, our study revealed the important roles and underlying molecular mechanisms of lncCAMTA1 on HCC, and suggested that lncCAMTA1 could be an effective prognostic factor and a potential therapeutic target for HCC.
Department of Radio-Oncology, First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, China. dinglijuanjl@163.com.
Li-Juan
LJ
Ding
Academy of Laboratory, Jilin Medical University, No. 5 Jilin Street, Jilin 132013, China. yanli1986jl@sina.com.
Yan
Y
Li
Center of Cardiovascular Diseases, First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, China. wangshudongjl@163.com.
Shu-Dong
SD
Wang
Department of Interventional Therapy, First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, China. xinsenwang3@126.com.
Xin-Sen
XS
Wang
Academy of Laboratory, Jilin Medical University, No. 5 Jilin Street, Jilin 132013, China. fangjifang2@sina.com.
Fang
F
Fang
Department of Pathology, Jilin Medical University, No. 5 Jilin Street, Jilin 132013, China. wangweiyao2@sina.cn.
Wei-Yao
WY
Wang
Department of Pathology, Jilin Medical University, No. 5 Jilin Street, Jilin 132013, China. penglv32@sina.cn.
Peng
P
Lv
Department of Pathology, Jilin Medical University, No. 5 Jilin Street, Jilin 132013, China. zhaodong_hai@sina.com.
Dong-Hai
DH
Zhao
Department of Hepatobiliary and Pancreas Surgery, First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, China. wei_feng@jlu.edu.cn.
Feng
F
Wei
Department of Pathology, Jilin Medical University, No. 5 Jilin Street, Jilin 132013, China. qiling@jlmpc.cn.
Ling
L
Qi
D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000737:chemistry; D016208:Databases, Factual; D018572:Disease-Free Survival; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
C487554:CAMTA1 protein, human; D002135:Calcium-Binding Proteins; D002843:Chromatin; D016376:Oligonucleotides, Antisense; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D015534:Trans-Activators
CAMTA1; cancer stem cells; liver cancer; long noncoding RNA; tumorigenesis
J Clin Invest. 2010 Sep;120(9):3326-39
20697159
Int J Mol Sci. 2015 Feb 03;16(2):3251-66
25654223
Gastroenterology. 2007 Jun;132(7):2542-56
17570225
Cancer Cell. 2014 May 12;25(5):666-81
24768205
Tumour Biol. 2016 May;37(5):5765-8
26206498
Cancer Cell. 2015 Oct 12;28(4):529-40
26461095
Biomed Pharmacother. 2016 May;80:73-9
27133041
J Hepatol. 2015 Nov;63(5):1164-72
26095183
Hepatology. 2015 Nov;62(5):1480-96
26185016
J Hepatol. 2016 Jun;64(6):1283-94
26812074
Nat Genet. 2013 Nov;45(11):1392-8
24076601
Tumour Biol. 2016 Jan;37(1):201-9
26188902
Nat Cell Biol. 2009 Dec;11(12 ):1487-95
19935649
Int J Mol Sci. 2014 Jun 03;15(6):9894-906
24897024
Tumour Biol. 2016 Feb;37(2):1617-25
26304505
Int J Mol Sci. 2013 Apr 25;14(5):9099-110
23698766
Int J Mol Sci. 2013 Oct 16;14 (10 ):20768-92
24135872
Cell Stem Cell. 2012 Jun 14;10(6):717-28
22704512
Nature. 2015 May 14;521(7551):232-6
25915022
Int J Mol Sci. 2013 Feb 21;14(2):4298-316
23429271
Hepatology. 2016 Jul;64(1):117-29
26910875
Mol Cell. 2015 Nov 19;60(4):626-36
26590717
Nature. 2014 Dec 4;516(7529):S2-3
25470197
Am J Transl Res. 2012;4(2):127-50
22611467
Cancer Res. 2011 Apr 15;71(8):3142-51
21385898
Prev Chronic Dis. 2008 Jul;5(3):A74
18558024
J Mol Med (Berl). 2014 Apr;92(4):337-46
24531795
Cell Stem Cell. 2015 Apr 2;16(4):413-25
25842979
FEBS J. 2014 Feb;281(3):802-13
24397586
Nat Cell Biol. 2016 Apr;18(4):431-42
26999735
Mol Cell. 2014 Jun 5;54(5):716-27
24905005
Lung Cancer. 2014 Mar;83(3):411-5
24461304
Nat Cell Biol. 2012 Nov;14(11):1203-11
23041974
CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
21296855
Nat Rev Gastroenterol Hepatol. 2014 Nov;11(11):645-7
25245016
Cell Stem Cell. 2011 Jul 8;9(1):50-63
21726833
Hepatology. 2014 Oct;60(4):1278-90
25043274
J Exp Med. 2014 Sep 22;211(10):2119-34
25225459
EMBO J. 2011 Aug 19;30(20):4309-22
21857646
Nature. 2010 Apr 15;464(7291):1071-6
20393566
Cancer Cell. 2014 Nov 10;26(5):722-37
25517750