Identification of novel LncRNA targeting Smad2/PKCα signal pathway to negatively regulate malignant progression of glioblastoma
Identification of novel LncRNA targeting Smad2/PKCα signal pathway to negatively regulate malignant progression of glioblastoma
复制标题
鉴定靶向 Smad2/PKCα 信号通路的新型 LncRNA 以负向调节胶质母细胞瘤的恶性进展
DOI：
10.1002/jcp.29278
复制
发表时间：
2019-10
期刊：
影响因子：
--
通讯作者：
Gao DS
中科院分区：
文献类型：
--
作者：
Tang CX;Wang Y;Zhang L;Wang J;Wang W;Han X;Mu CY;Gao DS
多形性胶质母细胞瘤（GBM）是一种预后普遍较差的高增殖性肿瘤，越来越多的证据强调了长链非编码rna （lncRNAs）在胶质瘤细胞生物学行为中的潜力。本研究的重点是鉴定lncrna，以确定GBM可能预后的靶标。微阵列表达谱分析发现，在GBM中有1,759个lncRNA和3,026个mrna表达上调，1932个lncRNA和2,979个mrna表达下调。生物信息学分析和实验验证鉴定出tcon_00020456 （TCON）进行进一步分析。原位杂交、免疫组织化学和受体操作特征分析确定TCON（截断值= 3.5）在GBM中具有高度敏感性和特异性。分析不同lncRNA染色评分的IV级胶质瘤患者寿命。TCON评分低于3.5表示预后不良（生存期为0.25至7个月），即使手术切除了胶质瘤。TCON在GBM中显著降低，并与Smad2和PKCα蛋白激酶存在共表达关系。过表达TCON一方面减少了细胞的增殖，另一方面减少了细胞的迁移、侵袭。根据裸鼠致瘤性实验，TCON还能抑制体内上皮-间质转化和胶质瘤的进展。此外，我们通过RACE预测试和生物信息学分析预测了靶向Smad2、PKCα和TCON的microrna的潜在结合位点和交叉点。综上所述，TCON作为肿瘤抑制因子，靶向Smad2/PKCα轴，在抑制胶质瘤恶性进展中发挥了新的作用。此外，该研究还表明TCON水平可作为GBM的预后和诊断生物标志物。
Glioblastoma multiforme (GBM) is a highly proliferative cancer with generally poor prognosis and accumulating evidence has highlighted the potential of long noncoding RNAs (lncRNAs) in the biological behaviors of glioma cells. This study focused on the identification of lncRNAs to identify targets for possible GBM prognosis. Microarray expression profiling found that 1,759 lncRNAs and 3,026 messenger RNAs (mRNAs) were upregulated, and 1932s lncRNA and 2,979 mRNAs were downregulated in GBM. Bioinformatics analysis and experimental verification identified TCONS_00020456 (TCON) for further analysis. In situ hybridization, along with immunohistochemical and receiver operating characteristic analysis determined TCON (truncation value = 3.5) as highly sensitive and specific in GBM. Grade IV patients with glioma life span with different lncRNA staining scores were analyzed. TCON staining scores below 3.5 indicated poor prognosis (life span ranging from 0.25 to 7 months), even if the glioma was surgically removed. TCON decreased significantly in GBM, and showed a coexpressional relationship with Smad2 and protein kinase C α (PKCα). Overexpression of TCON reduced the proliferation on one hand and migration, invasion on the other. TCON also inhibited epithelial–mesenchymal transformation and glioma progression in vivo, based on a nude mouse tumorigenicity assay. In addition, we predicted a potential binding site and intersection that microRNAs targeting Smad2, PKCα, and TCON through RACE pretest and bioinformatics analysis. Taken together, TCON, regarded as oncosuppressor, targeting the Smad2/PKCα axis plays a novel role in inhibiting the malignant progression of glioma. Moreover, it also demonstrates that the level of TCON can be used as a prognostic and diagnostic biomarker for GBM.
登录
查看更多内容
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
64.5
作者：
Antal CE;Hudson AM;Kang E;Zanca C;Wirth C;Stephenson NL;Trotter EW;Gallegos LL;Miller CJ;Furnari FB;Hunter T;Brognard J;Newton AC
通讯作者：
Newton AC
CUEDC2通过抑制STAT3和NF-κB信号通路的激活来抑制胶质瘤致瘤性
影响因子：
5.2
作者：
Li F;Tang C;Jin D;Guan L;Wu Y;Liu X;Wu X;Wu QY;Gao D
通讯作者：
Gao D
一种新型的细胞周期相关 lncRNA HOXA11-AS 从 HOXA 转录物的 5 引物末端转录而来，是神经胶质瘤进展的生物标志物。
影响因子：
9.7
作者：
Wang Q;Zhang J;Liu Y;Zhang W;Zhou J;Duan R;Pu P;Kang C;Han L
通讯作者：
Han L
影响因子：
11.2
作者：
R. Mandil;E. Ashkenazi;M. Blass;I. Kronfeld;G. Kazimirsky;G. Rosenthal;F. Umansky;P. Lorenzo;P. Blumberg;C. Brodie
通讯作者：
R. Mandil;E. Ashkenazi;M. Blass;I. Kronfeld;G. Kazimirsky;G. Rosenthal;F. Umansky;P. Lorenzo;P. Blumberg;C. Brodie