Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic valu...Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.展开更多
基金supported by the Nature Science Foundation of Chongqing(Nos.cstc2016jcyjA0838 and cstc2020jcyj-msxmX0376).
文摘Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.
文摘目的运用全外显子测序(whole exome sequencing,WES)技术检测我国视网膜母细胞瘤(retinoblastoma,Rb)患者的关键突变基因,并通过生物学功能研究探索该基因在Rb进展中发挥的功能作用。方法对我国82例RB1基因突变阴性(RB1-/-)的Rb患者血液样本行WES筛选罕见突变基因;进一步检测基因罕见突变位点所引起的编码蛋白表达改变情况;构建敲低和过表达上述基因的体外、体内模型,观察其对Rb细胞增殖、迁移功能和肿瘤大小的影响。结果运用WES和罕见突变富集分析[SNP-set(sequence)kernel association test,SKAT],我们在RB1-/-的Rb患者中发现PLK3基因的罕见突变(Y318H),Y318H是一种致病性突变。转染突变质粒(Y318H)的Rb细胞株PLK3蛋白表达量减低。敲低PLK3促进Rb细胞的增殖和迁移,而过表达PLK3抑制Rb细胞的增殖和迁移。同时,PLK3表达改变可调控小鼠Rb皮下瘤的生长。结论PLK3基因罕见突变(Y318H)是我国患者Rb进展的重要致病因素,Y318H突变可介导PLK3蛋白表达减低,继而促进Rb细胞增殖和迁移,最终导致Rb的生长。上述研究表明PLK3基因突变可作为Rb早期筛查的分子标志物,为疾病的诊疗提供新靶点。
