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长链非编码RNA通过干扰p53与SART3-USP15复合物之间的相互作用诱导p53降解。

LncRNA induces p53 degradation by interfering with the interaction between p53 and the SART3-USP15 complex.

作者信息

Taniue Kenzui, Oda Takeaki, Hayashi Tomoatsu, Kamoshida Yuki, Takeda Yasuko, Sugawara Anzu, Shimoura Yuki, Negishi Lumi, Nagashima Takeshi, Okada-Hatakeyama Mariko, Kawamura Yoshifumi, Goshima Naoki, Akimitsu Nobuyoshi, Akiyama Tetsu

机构信息

Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.

Isotope Science Center, The University of Tokyo, Tokyo 113-0032, Japan.

出版信息

PNAS Nexus. 2023 Jul 4;2(7):pgad220. doi: 10.1093/pnasnexus/pgad220. eCollection 2023 Jul.

Abstract

Mammalian genomes encode large number of long noncoding RNAs (lncRNAs) that play key roles in various biological processes, including proliferation, differentiation, and stem cell pluripotency. Recent studies have addressed that some lncRNAs are dysregulated in human cancers and may play crucial roles in tumor development and progression. Here, we show that the lncRNA is required for the proliferation and tumorigenicity of colon cancer cells with wild-type p53. knockdown leads to decreased ubiquitination and stabilization of p53 protein. Moreover, we demonstrate that needs to interact with SART3 to destabilize p53 and to promote the proliferation and tumorigenicity of colon cancer cells. We further show that SART3 is associated with the ubiquitin-specific peptidase USP15 and that may induce p53 destabilization by inhibiting this interaction. These results suggest that interferes with the SART3-USP15 complex-mediated stabilization of p53 protein and thereby plays important roles in the proliferation and tumorigenicity of colon cancer cells. Our findings suggest that may be a promising molecular target for the therapy of colon cancer.

摘要

哺乳动物基因组编码大量长链非编码RNA(lncRNAs),它们在各种生物学过程中发挥关键作用,包括增殖、分化和干细胞多能性。最近的研究表明,一些lncRNAs在人类癌症中表达失调,可能在肿瘤发生和发展中起关键作用。在这里,我们表明lncRNA对于具有野生型p53的结肠癌细胞的增殖和致瘤性是必需的。敲低该lncRNA会导致p53蛋白的泛素化减少和稳定性增加。此外,我们证明该lncRNA需要与SART3相互作用,以使p53不稳定,并促进结肠癌细胞的增殖和致瘤性。我们进一步表明,SART3与泛素特异性肽酶USP15相关,并且该lncRNA可能通过抑制这种相互作用来诱导p53不稳定。这些结果表明,该lncRNA干扰了SART3-USP15复合物介导的p53蛋白稳定性,从而在结肠癌细胞的增殖和致瘤性中发挥重要作用。我们的研究结果表明,该lncRNA可能是结肠癌治疗的一个有前景的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f36d/10337854/7184267e3c33/pgad220f1.jpg

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