A key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Epigenetics Pub Date : 2023-12-01 Epub Date: 2022-12-07 DOI:10.1080/15592294.2022.2148433
Wangjin Xu, Weiyang Lou, Linhang Mei
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引用次数: 3

Abstract

Pancreatic adenocarcinoma is one of the leading lethal human cancer types and is notorious for its poor prognosis. A series of bioinformatic analyses and experimental validations were employed to explore the role and mechanism of pseudogene-derived RNAs in pancreatic adenocarcinoma. Consequently, a total of 13 upregulated and 7 downregulated pseudogene-derived RNAs in pancreatic adenocarcinoma were identified. Survival analysis revealed a statistically predictive role of AK4P1 for unfavourable prognosis of patients with pancreatic adenocarcinoma. Subcellular location analysis indicated that AK4P1 was mainly located in cytoplasm, in which AK4P1 might competitively bind to tumour suppressive miR-375 in pancreatic adenocarcinoma. Further analysis showed that SP1 was a potential downstream target gene of miR-375 in pancreatic adenocarcinoma. Intriguingly, expression determination validated that SP1 could positively regulate AK4P1 levels in pancreatic adenocarcinoma. Finally, AK4P1 might also exert its effects by interacting with oncogenic parental gene AK4 in pancreatic adenocarcinoma. Conclusively, the present study elucidated a key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.

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关键调控环AK4P1/miR-375/SP1在胰腺腺癌中的作用。
胰腺癌是人类癌症的主要致死类型之一,因其预后不良而臭名昭著。采用一系列生物信息学分析和实验验证来探索假基因衍生RNA在胰腺癌中的作用和机制。因此,在胰腺癌中总共鉴定出13个上调和7个下调的假基因衍生RNA。生存分析显示AK4P1对胰腺癌患者的不良预后具有统计学预测作用。亚细胞定位分析表明,AK4P1主要位于细胞质中,其中AK4P1可能与胰腺癌中的肿瘤抑制性miR-375竞争性结合。进一步的分析表明SP1是胰腺癌中miR-375的潜在下游靶基因。有趣的是,表达测定证实SP1可以正向调节胰腺癌中的AK4P1水平。最后,AK4P1也可能通过与胰腺癌的致癌亲代基因AK4相互作用而发挥其作用。总之,本研究阐明了胰腺癌中关键的调节环AK4P1/miR-375/SP1。
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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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