Down regulation of lincRNA-p21 contributes to gastric cancer development through Hippo-independent activation of YAP.
Down regulation of lincRNA-p21 contributes to gastric cancer development through Hippo-independent activation of YAP.
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lincRNA-p21 的下调通过 Hippo 独立的 YAP 激活促进胃癌的发展
DOI：
10.18632/oncotarget.19130
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Bi F
中科院分区：
文献类型：
--
作者：
Chen Y;Wei G;Xia H;Yu H;Tang Q;Bi F
长基因间隔型非编码RNA p21(lincRNA-p21)被认为是p53的直接转录靶点，在多种人类实体瘤中表达下调。然而，对lincRNA-p21在胃癌中的作用知之甚少。采用定量逆转录聚合酶链式反应(qRT-PCR)检测lincRNA-p21在组织和细胞系中的表达水平。将针对lincRNA-p21的siRNAs和对照siRNAs分别导入MGC-803和MKN-45细胞，观察lincRNA-p21表达降低对肿瘤发生的影响。我们还在MGC-803细胞中过表达了lincRNA-p21。采用CCK-8和乙炔-2-脱氧尿苷(EDU)掺入法检测细胞增殖。通过创面愈合和Transwell实验检测细胞的迁移和侵袭能力。与正常组织相比，胃癌组织中lincRNA-p21的表达水平显著降低(p<；0.001)，并且这种降低水平与胃癌的侵袭深度分级(p=0.024)、远处转移(p=0.009)和分期(p=0.011)显著相关。进一步研究发现，lincRNA-p21基因敲除可促进胃癌细胞的恶性行为，并诱导上皮细胞向间充质细胞转化。过表达lincRNA-p21则表现出相反的作用。此外，下调lincRNA-p21可以通过提高HIPPO信号的核心效应蛋白YAP的表达水平，增加其核转位，而不是经典的HIPPO途径。过表达实验证实了lincRNA-p21在YAP表达中的调控作用。总之，这些数据表明lincRNA-p21可以作为一个潜在的生物标记物和胃癌的重要治疗靶点。
Long intergenic non-coding RNA p21 (lincRNA-p21), known as the direct transcriptional target of p53, was found down-regulated in several human solid tumors. However, little is known about the role of lincRNA-p21 in gastric cancer. The expression levels of lincRNA-p21 in tissue samples and cell lines were detected by qRT-PCR. MGC-803 and MKN-45 cells were transfected with siRNAs targeting lincRNA-p21 or control siRNAs to determine the effect of reduced lincRNA-p21 expression on tumorigenesis. We also overexpressed lincRNA-p21 in MGC-803 cells. Cell proliferation was measured by CCK-8 and Ethynyl-2-deoxyuridine (EdU) incorporation assays. Migration and invasion abilities of cells were measured by wound healing and transwell assay. We demonstrated that lincRNA-p21 was significantly reduced in gastric cancer tissues (p<0.001) compared with that in normal tissues and this lower level of lincRNA-p21 was significantly correlated with higher invasion depth grade (p=0.024), more distant metastasis (p=0.009) and advanced TNM stage (p=0.011). Further study revealed that knock down of lincRNA-p21 could promote malignant behavior of gastric cancer cells and induce epithelial to mesenchymal transition (EMT). Overexpressing lincRNA-p21 showed opposite effects. Moreover, knocking down lincRNA-p21 could elevate the expression of Yes associated protein (YAP), the core effector of Hippo signaling, by elevating mRNA levels and increasing its nucleus translocation instead of the canonical Hippo pathway. Overexpression experiments verified the regulation role of lincRNA-p21 in YAP expression. Collectively, these data suggest that lincRNA-p21 could serve as a potential biomarker and a vital therapeutic target in gastric cancer.
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影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.8
作者：
通讯作者：
--
长非编码 RNA MALAT-1 增强胰腺癌细胞中的干细胞样表型。
影响因子：
5.6
作者：
Jiao F;Hu H;Han T;Yuan C;Wang L;Jin Z;Guo Z;Wang L
通讯作者：
Wang L
影响因子：
9.3
作者：
Kim, Young-Il;Kim, Young-Woo;Kook, Myeong-Cheorl
通讯作者：
Kook, Myeong-Cheorl
DOI：
10.1016/j.urolonc.2010.01.005
发表时间：
2012-03-01
影响因子：
2.7
作者：
Muramaki, Mototsugu;Miyake, Hideaki;Fujisawa, Masato
通讯作者：
Fujisawa, Masato