MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor
MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.
Vyšlo v časopise:
MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor. PLoS Genet 6(3): e32767. doi:10.1371/journal.pgen.1000879
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000879
Souhrn
MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.
Zdroje
1. OueN
AungPP
MitaniY
KuniyasuH
NakayamaH
2005 Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression. Oncology 69 Suppl 1 17 22
2. GuptaGP
MassagueJ
2006 Cancer metastasis: building a framework. Cell 127 679 695
3. KleinCA
2008 Cancer. The metastasis cascade. Science 321 1785 1787
4. SteegPS
2006 Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12 895 904
5. NicolosoMS
SpizzoR
ShimizuM
RossiS
CalinGA
2009 MicroRNAs - the micro steering wheel of tumour metastases Nat Rev Cancer
6. MaL
Teruya-FeldsteinJ
WeinbergRA
2007 Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449 682 688
7. HuangQ
GumireddyK
SchrierM
le SageC
NagelR
2008 The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10 202 210
8. LeeDY
DengZ
WangCH
YangBB
2007 MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci U S A 104 20350 20355
9. GregoryPA
BertAG
PatersonEL
BarrySC
TsykinA
2008 The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10 593 601
10. WuH
ZhuS
MoYY
2009 Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res
11. HurstDR
EdmondsMD
ScottGK
BenzCC
VaidyaKS
2009 Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 69 1279 1283
12. PrueittRL
YiM
HudsonRS
WallaceTA
HoweTM
2008 Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer. Prostate 68 1152 1164
13. LiT
LiD
ShaJ
SunP
HuangY
2009 MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem Biophys Res Commun
14. SenguptaS
den BoonJA
ChenIH
NewtonMA
StanhopeSA
2008 MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A 105 5874 5878
15. VeerlaS
LindgrenD
KvistA
FrigyesiA
StaafJ
2009 MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 124 2236 2242
16. SeguraMF
HannifordD
MenendezS
ReavieL
ZouX
2009 Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A 106 1814 1819
17. NassD
RosenwaldS
MeiriE
GiladS
Tabibian-KeissarH
2008 MiR-92b and miR-9/9* Are Specifically Expressed in Brain Primary Tumors and Can Be Used to Differentiate Primary from Metastatic Brain Tumors. Brain Pathol
18. AsanganiIA
RasheedSA
NikolovaDA
LeupoldJH
ColburnNH
2008 MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27 2128 2136
19. LewisBP
BurgeCB
BartelDP
2005 Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120 15 20
20. LaiEC
2002 Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30 363 364
21. KloostermanWP
PlasterkRH
2006 The diverse functions of microRNAs in animal development and disease. Dev Cell 11 441 450
22. Esquela-KerscherA
SlackFJ
2006 Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 6 259 269
23. LuJ
GetzG
MiskaEA
Alvarez-SaavedraE
LambJ
2005 MicroRNA expression profiles classify human cancers. Nature 435 834 838
24. VoliniaS
CalinGA
LiuCG
AmbsS
CimminoA
2006 A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103 2257 2261
25. MartinezI
GardinerAS
BoardKF
MonzonFA
EdwardsRP
2008 Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene 27 2575 2582
26. PetroccaF
VisoneR
OnelliMR
ShahMH
NicolosoMS
2008 E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13 272 286
27. YanaiharaN
CaplenN
BowmanE
SeikeM
KumamotoK
2006 Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9 189 198
28. LeiteKR
Sousa-CanavezJM
ReisST
TomiyamaAH
Camara-LopesLH
2009 Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis. Urol Oncol
29. HeXX
YangJ
DingYW
LiuW
ShenQY
2006 Increased epithelial and serum expression of macrophage migration inhibitory factor (MIF) in gastric cancer: potential role of MIF in gastric carcinogenesis. Gut 55 797 802
30. WangB
XiaoY
DingB-B
ZhangN
YuanX-b
2003 Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 4 19 29
31. SuchtingS
HealP
TahtisK
StewartLM
BicknellR
2005 Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration. FASEB J 19 121 123
32. GroneJ
DoeblerO
LoddenkemperC
HotzB
BuhrHJ
2006 Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer. Oncol Rep 15 1437 1443
33. ItoH
FunahashiS
YamauchiN
ShibaharaJ
MidorikawaY
2006 Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target. Clin Cancer Res 12 3257 3264
34. LeeCH
FangCY
SheuJJ
ChangY
TakadaK
2008 Amplicons on chromosome 3 contain oncogenes induced by recurrent exposure to 12-O-tetradecanoylphorbol-13-acetate and sodium n-butyrate and Epstein-Barr virus reactivation in a nasopharyngeal carcinoma cell line. Cancer Genet Cytogenet 185 1 10
35. LeggJA
HerbertJM
ClissoldP
BicknellR
2008 Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration. Angiogenesis 11 13 21
36. MertschS
SchmitzN
JeibmannA
GengJG
PaulusW
2008 Slit2 involvement in glioma cell migration is mediated by Robo1 receptor. J Neurooncol 87 1 7
37. SchmidBC
RezniczekGA
FabjaniG
YonedaT
LeodolterS
2007 The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells. Breast Cancer Res Treat 106 333 342
38. GramantieriL
FerracinM
FornariF
VeroneseA
SabbioniS
2007 Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 67 6092 6099
39. SethP
LinY
HanaiJ
ShivalingappaV
DuyaoMP
2005 Magic roundabout, a tumor endothelial marker: expression and signaling. Biochem Biophys Res Commun 332 533 541
40. AbdollahiA
SchwagerC
KleeffJ
EspositoI
DomhanS
2007 Transcriptional network governing the angiogenic switch in human pancreatic cancer. Proc Natl Acad Sci U S A 104 12890 12895
41. ShiXB
TepperCG
WRW
2008 Cancerous miRNAs and their regulation. Cell Cycle 7 1529 1538
42. LinSL
MillerJD
YingSY
2006 Intronic MicroRNA (miRNA). J Biomed Biotechnol 2006: 26818. 26818
43. ChuYW
YangPC
YangSC
ShyuYC
HendrixMJ
1997 Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 17 353 360
44. WangCC
TsaiMF
DaiTH
HongTM
ChanWK
2007 Synergistic activation of the tumor suppressor, HLJ1, by the transcription factors YY1 and activator protein 1. Cancer Res 67 4816 4826
45. TsengRC
LinRK
WenCK
TsengC
HsuHS
2008 Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type beta-catenin nuclear accumulation in lung tumorigenesis. Oncogene 27 4488 4496
46. ChangDK
LinCT
WuCH
WuHC
2009 A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer. PLoS ONE 4 e4171 doi:10.1371/journal.pone.0004171
47. TorngPL
LeeYC
HuangCY
YeJH
LinYS
2008 Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma. Oncogene 27 2137 2147
48. YuSL
ChenHY
ChangGC
ChenCY
ChenHW
2008 MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 13 48 57
49. ZhuS
WuH
WuF
NieD
ShengS
2008 MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18 350 359
50. HiyoshiY
KamoharaH
KarashimaR
SatoN
ImamuraY
2009 MicroRNA-21 Regulates the Proliferation and Invasion in Esophageal Squamous Cell Carcinoma. Clin Cancer Res
51. CrawfordM
BrawnerE
BatteK
YuL
HunterMG
2008 MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun 373 607 612
52. TavazoieSF
AlarconC
OskarssonT
PaduaD
WangQ
2008 Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451 147 152
53. LiN
FuH
TieY
HuZ
KongW
2009 miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett 275 44 53
54. GebeshuberCA
ZatloukalK
MartinezJ
2009 miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep
55. DalmayT
EdwardsDR
2006 MicroRNAs and the hallmarks of cancer. Oncogene 25 6170 6175
56. HuminieckiL
GornM
SuchtingS
PoulsomR
BicknellR
2002 Magic Roundabout Is a New Member of the Roundabout Receptor Family That Is Endothelial Specific and Expressed at Sites of Active Angiogenesis. Genomics 79 547 552
57. BroseK
Tessier-LavigneM
2000 Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr Opin Neurobiol 10 95 102
58. KiddT
BroseK
MitchellKJ
FetterRD
Tessier-LavigneM
1998 Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92 205 215
59. ZallenJA
YiBA
BargmannCI
1998 The conserved immunoglobulin superfamily member SAX-3/Robo directs multiple aspects of axon guidance in C. elegans. Cell 92 217 227
60. DicksonBJ
GilestroGF
2006 Regulation of commissural axon pathfinding by slit and its Robo receptors. Annu Rev Cell Dev Biol 22 651 675
61. BhatKM
GaziovaI
KrishnanS
2007 Regulation of axon guidance by slit and netrin signaling in the Drosophila ventral nerve cord. Genetics 176 2235 2246
62. WuJY
FengL
ParkHT
HavliogluN
WenL
2001 The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 410 948 952
63. GuanH
ZuG
XieY
TangH
JohnsonM
2003 Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses. J Immunol 171 6519 6526
64. PrasadA
QamriZ
WuJ
GanjuRK
2007 Slit-2/Robo-1 modulates the CXCL12/CXCR4-induced chemotaxis of T cells. J Leukoc Biol 82 465 476
65. RossiMR
HuntoonK
CowellJK
2005 Differential expression of the LGI and SLIT families of genes in human cancer cells. Gene 356 85 90
66. NarayanG
GoparajuC
Arias-PulidoH
KaufmannAM
SchneiderA
2006 Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. Mol Cancer 5 16
67. SinghRK
IndraD
MitraS
MondalRK
BasuPS
2007 Deletions in chromosome 4 differentially associated with the development of cervical cancer: evidence of slit2 as a candidate tumor suppressor gene. Hum Genet 122 71 81
68. PrasadA
ParuchuriV
PreetA
LatifF
GanjuRK
2008 Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells. J Biol Chem 283 26624 26633
69. DallolA
ForgacsE
MartinezA
SekidoY
WalkerR
2002 Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. Oncogene 21 3020 3028
70. XianJ
ClarkKJ
FordhamR
PannellR
RabbittsTH
2001 Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene. Proc Natl Acad Sci U S A 98 15062 15066
71. LatilA
CheneL
Cochant-PriolletB
ManginP
FournierG
2003 Quantification of expression of netrins, slits and their receptors in human prostate tumors. Int J Cancer 103 306 315
72. KimHK
ZhangH
LiH
WuTT
SwisherS
2008 Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. Neoplasia 10 1411 1420
73. JinJ
YouH
YuB
DengY
TangN
2009 Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas. Biochem Biophys Res Commun 379 86 91
74. AndrewsW
LiapiA
PlachezC
CamurriL
ZhangJ
2006 Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain. Development 133 2243 2252
75. LiuJ
ZhangL
WangD
ShenH
JiangM
2003 Congenital diaphragmatic hernia, kidney agenesis and cardiac defects associated with Slit3-deficiency in mice. Mech Dev 120 1059 1070
76. BarikS
2008 An intronic microRNA silences genes that are functionally antagonistic to its host gene. Nucleic Acids Res 36 5232 5241
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