lncSLERT Promotes Liver Metastasis in Colorectal Cancer by Down-Regulating HUNK Expression via RBM15-Mediated m6A Modification.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-05-09 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S514001

Lin Wang, Liming Zhao, Jialiang Liu, Pu Cheng, Mingyu Han, Zhaoxu Zheng

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引用次数: 0

Abstract

Background: Metastasis is a hallmark of cancer and the leading cause of cancer-related mortality. However, the mechanism underlying liver metastasis in colorectal cancer (CRC) remains incompletely understood. This study explores the role of long non-coding RNA (lncRNA) SLERT in promoting CRC liver metastasis by downregulating HUNK expression.

Methods: SLERT expression levels in CRC tissues were analyzed and correlated with patient survival outcomes. Functional assays, including migration and invasion assays, were performed to assess the impact of SLERT knockdown and overexpression on metastatic behavior. Mechanistic studies examined SLERT's interaction with the RNA-binding protein RBM15 and its effect on HUNK mRNA stability. The subcellular localization of SLERT was also determined.

Results: SLERT was significantly upregulated in CRC tissues and associated with poor survival outcomes. Silencing SLERT inhibited CRC cell migration and invasion, whereas its overexpression enhanced these metastatic properties. Mechanistically, SLERT interacted with RBM15, impairing its ability to stabilize HUNK mRNA, leading to decreased HUNK expression and increased metastatic potential. SLERT was primarily localized in the cytoplasm, indicating its active role in gene regulation within the tumor microenvironment.

Conclusion: LERT promotes liver metastasis in CRC by downregulating HUNK expression through RBM15-mediated mRNA destabilization. These findings suggest that SLERT could serve as a diagnostic biomarker and therapeutic target. Targeting SLERT or restoring HUNK expression may provide novel strategies to combat CRC liver metastasis and improve patient prognosis.

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lncSLERT通过rbm15介导的m6A修饰下调HUNK表达促进结直肠癌肝转移。

背景：转移是癌症的标志，也是癌症相关死亡的主要原因。然而，结直肠癌（CRC）肝转移的机制仍不完全清楚。本研究探讨长链非编码RNA (lncRNA) SLERT通过下调HUNK表达促进结直肠癌肝转移的作用。方法：分析结直肠癌组织中SLERT表达水平及其与患者生存结果的相关性。功能测试，包括迁移和侵袭测试，评估SLERT敲低和过表达对转移行为的影响。机制研究检测了SLERT与rna结合蛋白RBM15的相互作用及其对HUNK mRNA稳定性的影响。同时确定了SLERT的亚细胞定位。结果：SLERT在结直肠癌组织中显著上调，并与较差的生存结果相关。沉默SLERT抑制结直肠癌细胞的迁移和侵袭，而其过表达则增强了这些转移性。从机制上讲，SLERT与RBM15相互作用，损害其稳定HUNK mRNA的能力，导致HUNK表达降低和转移潜力增加。SLERT主要定位于细胞质中，表明其在肿瘤微环境中具有积极的基因调控作用。结论：LERT通过rbm15介导的mRNA失稳，下调HUNK表达，促进结直肠癌肝转移。这些发现表明，SLERT可以作为一种诊断性生物标志物和治疗靶点。靶向SLERT或恢复HUNK表达可能提供对抗结直肠癌肝转移和改善患者预后的新策略。

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

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.