LncRNA expression profile of ΔNp63α in cervical squamous cancers and its suppressive effects on LIF expression
LncRNA expression profile of ΔNp63α in cervical squamous cancers and its suppressive effects on LIF expression
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宫颈鳞癌中Delta Np63 α的lncRNA表达谱及其对LIF表达的抑制作用
DOI：
10.1016/j.cyto.2017.04.001
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发表时间：
2017-08-01
期刊：
影响因子：
3.8
通讯作者：
Zhou, Ying
中科院分区：
文献类型：
--
作者：
Qian, Lili;Xu, Fei;Zhou, Ying
我们的目标是确定 Delta Np63 α 在宫颈癌中的 IncRNA 靶标以及癌分化中的分子程序。在过表达 p63 SiHa 细胞 (SiHa/Delta Np63 alpha) 和对照细胞系 (SiHa/pCon) 中分析和验证了 lncRNA 的不同特征。 ENST00000422259、ENST00000447565 (Lnc-LIF-AS) 和 ENST00000469965 及其相关反义 mRNA DPYD（二氢嘧啶脱氢酶，嘧啶分解代谢途径基因）、LIF（白血病抑制因子）和 FLNC（细丝蛋白 C）在两种细胞中均存在显着差异表达。 Delta Np63 α 过表达细胞和敲低细胞。在这里，我们证明了 Delta Np63 α 可以通过直接转录调控来抑制 LIF mRNA 的水平，并通过抑制 Lnc-LIF-AS 的表达来降低 LIF mRNA 的稳定性。 LIF 和 Delta Np63 α 表达的反向相互作用也在宫颈癌的临床样本中得到验证，宫颈癌中高水平的 LIF 与患者生存率较差有关。 Delta Np63 α的减少也减弱了宫颈癌细胞的分化。提示Delta Np63 α可能形成一个复杂的网络来调节宫颈癌的分化。
We aim to determine the IncRNA targets of Delta Np63 alpha in cervical cancer and molecular programs in cancerous differentiation. Different profiles of the lncRNAs were assayed and validated in overexpressing p63 SiHa cells (SiHa/Delta Np63 alpha) and the control cell lines (SiHa/pCon). ENST00000422259, ENST00000447565 (Lnc-LIF-AS) and ENST00000469965, together with their related antisense mRNA DPYD (dihydropyrimidine dehydrogenase, a pyrimidine catabolic pathway gene), LIF (leukemia inhibitor factor) and FLNC (filamin C) were all notably differentially expressed in both Delta Np63 alpha overexpression cells and knockdown cells. Here, we illustrated that Delta Np63 alpha can inhibit the levels of LIF mRNA by direct transcription regulation and decrease LIF mRNA stability by suppressing the expression of Lnc-LIF-AS. An inverse interaction of LIF and Delta Np63 alpha expression was as well validated in clinical samples of cervical cancer, and high level of LIF in cervical cancers was related with poor patient survival. The decrease of Delta Np63 alpha also attenuated the differentiation of cervical cancerous cells. Suggesting that Delta Np63 alpha may be form a complex network in regulation cervical cancerous differentiation.