UKLF/PCBP2 axis governs the colorectal cancer development by transcriptionally activating SLC39A4

IF 4.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research Pub Date : 2024-05-18 DOI:10.1016/j.bbamcr.2024.119755

Yunze Li, Lina Liu

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引用次数: 0

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignant tumors with limited treatment options. Therefore, there is an urgent need to investigate new therapeutic targets against CRC. Ubiquitous Kruppel-like factor (UKLF) is involved in various cancer processes, but its effect and detailed molecular mechanism in CRC are not yet fully understood. Here, this study aimed to investigate the function and mechanism of UKLF in the development of CRC. The results showed that UKLF was highly expressed in CRC tissues from clinical patients and its high expression was related to poor prognosis. UKLF promoted cell proliferation, migration and invasion, and inhibited cell apoptosis. The promotion effect of UKLF on tumor growth was further confirmed in vivo. As far as the mechanism was concerned, poly (C) binding protein 2 (PCBP2) was verified to bind to the 3′-UTR of UKLF mRNA and enhance its mRNA stability. Moreover, UKLF modulated the expression of solute carrier family 39 member 4 (SLC39A4) at the transcriptional level. Taken together, these findings elucidated the regulatory mechanism of UKLF and uncovered the importance of the PCBP2/UKLF/SLC39A4 pathway. The targeting of UKLF may be a novel direction for molecular-targeted CRC therapy.

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UKLF/PCBP2 轴通过转录激活 SLC39A4 来控制结直肠癌的发展。

结肠直肠癌（CRC）是发病率最高的恶性肿瘤之一，但治疗方案有限。因此，研究针对 CRC 的新治疗靶点迫在眉睫。Ubiquitous Kruppel-like factor（UKLF）参与多种癌症过程，但其在 CRC 中的作用和详细分子机制尚未完全清楚。本研究旨在探讨UKLF在CRC发病过程中的功能和机制。结果显示，UKLF在临床患者的CRC组织中高表达，且其高表达与预后不良有关。UKLF促进细胞增殖、迁移和侵袭，抑制细胞凋亡。UKLF对肿瘤生长的促进作用在体内得到了进一步证实。在机制方面，研究证实多聚（C）结合蛋白2（PCBP2）能与UKLF mRNA的3'-UTR结合，增强其mRNA的稳定性。此外，UKLF 在转录水平上调节了溶质运载家族 39 成员 4（SLC39A4）的表达。综上所述，这些发现阐明了UKLF的调控机制，并揭示了PCBP2/UKLF/SLC39A4通路的重要性。靶向UKLF可能是CRC分子靶向治疗的一个新方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular cell research 生物-生化与分子生物学

CiteScore

10.00

自引率

2.00%

发文量

151

审稿时长

44 days

期刊介绍： BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.