Abstract：
:Previous studies indicated that microRNA (miR)-675 and its precursor lncRNA H19 were both overexpressed in glioma tissues, and H19 might play an oncogenic role. To investigate the involvement of miR-675 in gliomas and its underlying mechanisms, we here collected candidate target genes of miR-675-5p from miRTarBase (http://mirtarbase.mbc.nctu.edu.tw/, Release 6.0), which contains the experimentally validated microRNA-target interactions. Then, regulatory effects of miR-675 on its target genes were validated using clinical samples and glioma cell lines. Involvement of the miR-675-target axis deregulation in cell proliferation, migration and invasion of glioma was demonstrated by both gain- and loss-of-function experiments. As a result, retinoblastoma 1 (RB1) was identified as a candidate target gene of miR-675-5p. Expression levels of miR-675-5p in glioma tissues and cells were negatively correlated with RB1 expression at both mRNA and protein levels. Importantly, deregulation of the miR-675-5p-RB1 axis was significantly associated with advanced World Health Organization (WHO) grade and low Karnofsky performance score (KPS) score of glioma patients. Luciferase reporter assay verified that RB1 was a direct target gene of miR-675 in glioma cells. Functionally, miR-675 promoted glioma cell proliferation, migration and invasion. Notably, simulation of RB1 antagonized the effects induced by miR-675 up-regulation in glioma cells. In conclusion, our data suggest that miR-675 may be a key negative regulator of RB1 and the imbalance of the miR-675-RB1 axis may be clinically associated with aggressive progression of glioma patients. In addition, miR-675 may act as an oncogenic miRNA in glioma cells via regulating its target gene RB1.
journal_name
Hum Patholjournal_title
Human pathologyauthors
Zheng Y,Lu X,Xu L,Chen Z,Li Q,Yuan Jdoi
10.1016/j.humpath.2017.09.006subject
Has Abstractpub_date
2017-11-01 00:00:00pages
63-71eissn
0046-8177issn
1532-8392pii
S0046-8177(17)30351-9journal_volume
69pub_type
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