研究动态
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胰腺癌中的关键调控环路AK4P1/miR-375/SP1。

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

发表日期:2023 Dec
作者: Wangjin Xu, Weiyang Lou, Linhang Mei
来源: Epigenetics

摘要:

胰腺癌腺癌是致命人类癌症类型之一,以其差劣预后而臭名昭著。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在胰腺腺癌中的作用和机制。因此,共鉴定了13个上调和7个下调的胰腺腺癌假基因衍生RNA。生存分析显示AK4P1在胰腺癌患者的不良预后中具有统计预测作用。亚细胞定位分析表明,在细胞质中,AK4P1可能与胰腺腺癌中的肿瘤抑制miR-375发生竞争性结合。进一步分析表明,在胰腺癌中,SP1是miR-375的潜在下游靶基因。有趣的是,表达确定验证了SP1可以积极地调节胰腺腺癌中的AK4P1水平。最后,AK4P1在胰腺癌中也可能通过与致癌的原代基因AK4相互作用发挥其效应。总之,本研究阐明了胰腺腺癌中关键的调节环AK4P1/miR-375/SP1。
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.