Qian Lili, Xu Fei, Wang Xiaolin, Jiang Ming, Wang Juan, Song Weiguo, Wu Dabao, Shen Zhen, Feng Dingqing, Ling Bin, Cheng Yong, Xiao Weihua, Shan Ge, Zhou Ying
Department of Obstetrics and Gynecology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China.
Cytokine. 2017 Aug;96:114-122. doi: 10.1016/j.cyto.2017.04.001. Epub 2017 Apr 7.
We aim to determine the lncRNA targets of ΔNp63α in cervical cancer and molecular programs in cancerous differentiation. Different profiles of the lncRNAs were assayed and validated in overexpressing p63 SiHa cells (SiHa/ΔNp63α) 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 ΔNp63α overexpression cells and knockdown cells. Here, we illustrated that ΔNp63α 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 ΔNp63α 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 ΔNp63α also attenuated the differentiation of cervical cancerous cells. Suggesting that ΔNp63α may be form a complex network in regulation cervical cancerous differentiation.
我们旨在确定ΔNp63α在宫颈癌中的lncRNA靶点以及癌分化中的分子程序。在过表达p63的SiHa细胞(SiHa/ΔNp63α)和对照细胞系(SiHa/pCon)中检测并验证了lncRNAs的不同谱。ENST00000422259、ENST00000447565(Lnc-LIF-AS)和ENST00000469965,以及它们相关的反义mRNA DPYD(二氢嘧啶脱氢酶,一种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ΔNp63α过表达细胞和敲低细胞中均有显著差异表达。在此,我们表明ΔNp63α可通过直接转录调控抑制LIF mRNA水平,并通过抑制Lnc-LIF-AS的表达降低LIF mRNA稳定性。LIF与ΔNp63α表达的反向相互作用在宫颈癌临床样本中也得到了验证,宫颈癌中LIF的高表达与患者预后不良相关。ΔNp63α的降低也减弱了宫颈癌细胞的分化。这表明ΔNp63α可能在调控宫颈癌分化中形成一个复杂的网络。