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山核桃作为一种竞争性内源性 RNA,在肺癌中与 S 期激酶相关蛋白 2 相互作用。

Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer.

机构信息

Department of Biochemistry and Molecular Biology, Medical School of Ningbo University, Ningbo, ZJ 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, ZJ 315211, China.

Department of Chest Surgery, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, ZJ 315020, China.

出版信息

Cancer Lett. 2017 Oct 10;406:36-46. doi: 10.1016/j.canlet.2017.07.030. Epub 2017 Aug 5.

DOI:10.1016/j.canlet.2017.07.030
PMID:28789966
Abstract

Investigating the RNA-RNA interactions involving in the initiation and progression of non-small cell lung cancer (NSCLC) may provide promising diagnostic and targeted therapeutic strategies. Here, we showed that pecanex (PCNX) positively regulates the mRNA and protein expressions of S-phase kinase associated protein 2 (Skp2) in miRNA- and 3' UTR-dependent manners. And miR-26, miR-182, miR-340 and miR-506 were verified as the common miRNAs shared by Skp2 and PCNX. Intriguingly, we initially uncovered that PCNX-3' UTR promotes cell growth, proliferation and cell cycle progression, and suppresses apoptosis of lung cancer cells, which is consistent with the oncogenic activity of Skp2-3' UTR. Consequently, PCNX was identified as a competitive endogenous RNA (ceRNA) of Skp2. Moreover, knockdown of PCNX inhibits EGF-induced Akt phosphorylation, which can be reversed by the silencing of Dicer. Finally, we further discovered that Skp2 and PCNX are coordinately upregulated in lung cancer tissues compared with the adjacent non-tumor tissues. Our study establishes for the first time the oncogenic property of PCNX-3' UTR and Skp2-3' UTR, and the PCNX-miRNA-Skp2 regulatory pattern, which may offer a molecular basis for the diagnosis and targeted therapy in NSCLC.

摘要

研究涉及非小细胞肺癌(NSCLC)发生和进展的 RNA-RNA 相互作用可能提供有前景的诊断和靶向治疗策略。在这里,我们表明 pecnex(PCNX)以 miRNA 和 3'UTR 依赖的方式正向调节 S 期激酶相关蛋白 2(Skp2)的 mRNA 和蛋白表达。miR-26、miR-182、miR-340 和 miR-506 被验证为 Skp2 和 PCNX 共有的常见 miRNA。有趣的是,我们最初发现 PCNX-3'UTR 促进肺癌细胞的生长、增殖和细胞周期进程,并抑制细胞凋亡,这与 Skp2-3'UTR 的致癌活性一致。因此,PCNX 被鉴定为 Skp2 的竞争性内源 RNA(ceRNA)。此外,PCNX 的敲低抑制了 EGF 诱导的 Akt 磷酸化,而 Dicer 的沉默可以逆转这种抑制。最后,我们进一步发现与相邻非肿瘤组织相比,Skp2 和 PCNX 在肺癌组织中协同上调。我们的研究首次建立了 PCNX-3'UTR 和 Skp2-3'UTR 的致癌特性,以及 PCNX-miRNA-Skp2 调控模式,这可能为 NSCLC 的诊断和靶向治疗提供分子基础。

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