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000177255 041__ $$aEnglish
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000177255 1001_ $$aHuang, Yulun$$b0
000177255 245__ $$aSpatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion.
000177255 260__ $$aWeinheim$$bWiley-VCH$$c2021
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000177255 500__ $$a2021 Dec;8(23):e2101923
000177255 520__ $$aDiffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasion have long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBMINV ) and tumor core (GBMTC ) cells from the brains of 6 highly invasive patient-derived orthotopic models is described. Direct comparison of these GBMINV and GBMTC cells reveals a significantly elevated invasion capacity in GBMINV cells, detects 23/768 miRNAs over-expressed in the GBMINV cells (miRNAINV ) and 22/768 in the GBMTC cells (miRNATC ), respectively. Silencing the top 3 miRNAsINV (miR-126, miR-369-5p, miR-487b) successfully blocks invasion of GBMINV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNAINV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4-aminopyridine (4-AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBMINV and GBMTC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis.
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000177255 650_7 $$2Other$$a4-aminopyridine
000177255 650_7 $$2Other$$aKCNA1
000177255 650_7 $$2Other$$aglioblastoma
000177255 650_7 $$2Other$$amiRNA
000177255 650_7 $$2Other$$apatient derived orthotopic xenograft
000177255 7001_ $$aQi, Lin$$b1
000177255 7001_ $$aKogiso, Mari$$b2
000177255 7001_ $$aDu, Yuchen$$b3
000177255 7001_ $$aBraun, Frank K$$b4
000177255 7001_ $$aZhang, Huiyuan$$b5
000177255 7001_ $$aHuang, L Frank$$b6
000177255 7001_ $$aXiao, Sophie$$b7
000177255 7001_ $$aTeo, Wan-Yee$$b8
000177255 7001_ $$aLindsay, Holly$$b9
000177255 7001_ $$aZhao, Sibo$$b10
000177255 7001_ $$aBaxter, Patricia$$b11
000177255 7001_ $$aSu, Jack M F$$b12
000177255 7001_ $$aAdesina, Adekunle$$b13
000177255 7001_ $$aYang, Jianhua$$b14
000177255 7001_ $$0P:(DE-He78)b0b3740107f746e09dc23fdf25eb0629$$aBrabetz, Sebastian$$b15
000177255 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b16$$udkfz
000177255 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b17$$udkfz
000177255 7001_ $$aChintagumpala, Murali$$b18
000177255 7001_ $$aPerlaky, Laszlo$$b19
000177255 7001_ $$aWang, Zhong$$b20
000177255 7001_ $$aZhou, Youxin$$b21
000177255 7001_ $$aMan, Tsz-Kwong$$b22
000177255 7001_ $$aLi, Xiao-Nan$$b23
000177255 773__ $$0PERI:(DE-600)2808093-2$$a10.1002/advs.202101923$$gp. 2101923 -$$n23$$pe2101923$$tAdvanced science$$v8$$x2198-3844$$y2021
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