Knockdown of STIL suppresses the progression of gastric cancer by down‐regulating the IGF‐1/PI3K/AKT pathway
Knockdown of STIL suppresses the progression of gastric cancer by down‐regulating the IGF‐1/PI3K/AKT pathway
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DOI:
10.1111/jcmm.14440
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发表时间:
2019
期刊:
影响因子:
--
通讯作者:
Xiangyang Xin
中科院分区:
文献类型:
--
作者:
Ju Wang;Yong Zhang;Zhongxia Dou;Hongwei Jiang;Yongqiang Wang;Xiaoping Gao;Xiangyang Xin
SCL/TAL1.interrupting.locus.(STIL).regulates.the.mitotic.centrosome.to.promote.the.centriolar.replication.and.cell.cycling,.and.is.associated.with.malignancies..However,.the.role.and.mechanism.of.STIL.in.gastric.cancer.(GC).remain.elusive..STIL.expres‐ sion.in.GC.tissue.microarray.was.detected.by.immunohistochemistry.(IHC)..GC.cells.were. transduced. with. control. lentivirus. or. lentivirus. for. expression. STIL‐specific.shRNA.and.the.effect.of.STIL.silencing.on.the.malignant.behaviors.of.GC.cells.was.measured in vitro and in vivo. The potential mechanisms underlying the action of STIL. were. analyzed. by. transcriptome. microarray. and. bioinformatics.. STIL. expres‐ sion was up‐regulated in GC tissues both in our cohort and the data from the can‐ cer genome atlas, and positively associated with T stage and poor overall survival of.GC.patients..Knockdown.of.STIL.significantly.inhibited.the.proliferation.and.clo‐ nogenicity of human GC cells and attenuated the growth of implanted GC in vivo. Furthermore,.STIL.silencing.induced.cell.cycle.arrest.in.G2/M.phase.and.apoptosis.of. GC. cells.. Transcriptome. analysis. indicated. that. STIL. silencing. modulated. many.gene.expression,.particularly.for.down‐regulating.the.IGF‐1/PI3K/AKT.pathway..In.addition,.treatment.with.SC79,.an.AKT.activator,.significantly.mitigated.the.effect.of.STIL‐silencing.in.GC.cells..In.conclusion,.STIL.promotes.gastric.carcinogenesis.and.progression.by.enhancing.the.IGF‐1/PI3K/AKT.signaling,.and.STIL.may.be.a.novel.target for intervention of GC.