MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6 and PIK3R2 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-09-22

AUTHORS

Chengli Du, Zhen Lv, Linping Cao, Chaofeng Ding, Owusu-ansah K Gyabaah, Haiyang Xie, Lin Zhou, Jian Wu, Shusen Zheng

ABSTRACT

BackgroundThe deregulation of microRNAs has been reported to play a pivotal role in hepatocellular carcinoma (HCC). MiR-126-3p has been reported to be associated with poor prognosis in HCC. However the underlying mechanism of miR-126-3p in HCC remains unclear.MethodsThe expression levels of miR-126-3p in HCC tissues and cells were detected by RT-PCR. Transwell assay and capillary tube formation assay were applied to assess the metastasis and angiogenesis in vitro. Nude mice subcutaneous tumor model was used to perform in vivo study. Dual- luciferase reporter assay was conducted to confirm the direct binding of miR-126-3p and target genes. The changes of biomarker protein levels were examined by western blot and Immunohistochemistry.ResultsWe observed that the miR-126-3p expression levels in HCC tissues and cells were significantly down-regulated. Through gain- and loss- of function studies, we showed that miR-126-3p dramatically inhibited HCC cells from migrating and invading extracellular matrix gel and suppressed capillary tube formation of endothelial cells in vitro. Furthermore, overexpression of miR-126-3p significantly reduced the volume of tumor and microvessel density in vivo. LRP6 and PIK3R2 were identified as targets of miR-126-3p. Silencing LRP6 and PIK3R2 had similar effects of miR-126-3p restoration on metastasis and angiogenesis individually in HCC cells. Furthermore, the miR-126-3p level was inversely correlated with LRP6 and PIK3R2 in HCC tissues. In addition, the rescue experiments indicated that the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2.ConclusionOur results demonstrates that deregulation of miR-126-3p contributes to metastasis and angiogenesis in HCC. The restoration of miR-126-3p expression may be a promising strategy for HCC therapy. More... »

PAGES

259

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12967-014-0259-1

DOI

http://dx.doi.org/10.1186/s12967-014-0259-1

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https://app.dimensions.ai/details/publication/pub.1050518943

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25240815


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35 schema:description BackgroundThe deregulation of microRNAs has been reported to play a pivotal role in hepatocellular carcinoma (HCC). MiR-126-3p has been reported to be associated with poor prognosis in HCC. However the underlying mechanism of miR-126-3p in HCC remains unclear.MethodsThe expression levels of miR-126-3p in HCC tissues and cells were detected by RT-PCR. Transwell assay and capillary tube formation assay were applied to assess the metastasis and angiogenesis in vitro. Nude mice subcutaneous tumor model was used to perform in vivo study. Dual- luciferase reporter assay was conducted to confirm the direct binding of miR-126-3p and target genes. The changes of biomarker protein levels were examined by western blot and Immunohistochemistry.ResultsWe observed that the miR-126-3p expression levels in HCC tissues and cells were significantly down-regulated. Through gain- and loss- of function studies, we showed that miR-126-3p dramatically inhibited HCC cells from migrating and invading extracellular matrix gel and suppressed capillary tube formation of endothelial cells in vitro. Furthermore, overexpression of miR-126-3p significantly reduced the volume of tumor and microvessel density in vivo. LRP6 and PIK3R2 were identified as targets of miR-126-3p. Silencing LRP6 and PIK3R2 had similar effects of miR-126-3p restoration on metastasis and angiogenesis individually in HCC cells. Furthermore, the miR-126-3p level was inversely correlated with LRP6 and PIK3R2 in HCC tissues. In addition, the rescue experiments indicated that the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2.ConclusionOur results demonstrates that deregulation of miR-126-3p contributes to metastasis and angiogenesis in HCC. The restoration of miR-126-3p expression may be a promising strategy for HCC therapy.
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41 schema:keywords HCC cells
42 HCC therapy
43 HCC tissues
44 LRP6
45 MethodsThe expression levels
46 PIK3R2
47 RT-PCR
48 ResultsWe
49 Western blot
50 addition
51 angiogenesis
52 angiogenesis function
53 binding
54 biomarker protein levels
55 blot
56 capillary tube formation
57 carcinoma
58 cells
59 changes
60 contributes
61 density
62 deregulation
63 deregulation of microRNAs
64 direct binding
65 dual-luciferase reporter
66 effect
67 endothelial cells
68 experiments
69 expression
70 expression levels
71 extracellular matrix gel
72 formation
73 function
74 function studies
75 gain
76 gel
77 genes
78 hepatocellular carcinoma
79 immunohistochemistry
80 levels
81 loss
82 matrix gel
83 mechanism
84 metastasis
85 miR-126-3p expression
86 miR-126-3p levels
87 microRNAs
88 microvessel density
89 model
90 mouse subcutaneous tumor model
91 nude mouse subcutaneous tumor model
92 overexpression
93 pivotal role
94 poor prognosis
95 prognosis
96 promising strategy
97 protein levels
98 reporter
99 rescue experiments
100 restoration
101 results
102 role
103 similar effects
104 strategies
105 study
106 subcutaneous tumor model
107 suppresses tumor metastasis
108 target
109 target genes
110 therapy
111 tissue
112 tube formation
113 tumor metastasis
114 tumor model
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119 volume
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