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环状异戊烯基半胱氨酸羧甲基转移酶上调并抑制膀胱癌的恶性行为。

circICMT upregulates and suppresses the malignant behavior of bladder cancer.

作者信息

Luo Xin, Xie FangMei, Qin Guoqiang, Zou Ge, Lu Xu, Zhang Chaofeng, Han Zeping, Zhao Ying, Song Xiaoyu, Luo WenFeng, Li Yongsheng, He JinHua, Shen Jian

机构信息

Department of Urology, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511400, PR China.

Central Laboratory, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511400, PR China.

出版信息

Transl Oncol. 2025 Feb;52:102262. doi: 10.1016/j.tranon.2024.102262. Epub 2024 Dec 28.

DOI:10.1016/j.tranon.2024.102262
PMID:39733742
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11743880/
Abstract

BACKGROUND

Circular RNA (circRNA) is a new type of endogenous single-stranded RNA with a covalently closed circular structure. Increasing evidence shows that circRNA plays an important role in regulating gene expression in tumors. circICMT is a circular RNA produced by the ICMT gene. Currently, the molecular function of circICMT in bladder cancer remains unclear.

METHOD

Differentially expressed circRNAs were identified from RNA sequencing data and circICMT was identified as a new candidate circRNA. qRT-PCR and sanger sequencing were used to detect the expression of circICMT in bladder cancer tissue specimens. Stable cell lines overexpressing and knocking down circICMT were constructed to explore the effect of circICMT on bladder cancer cells. Its biological effects were detected through wound healing experiments, colony formation experiments, CCK-8 experiments and xenogeneic tumorigenesis experiments.

RESULT

This study found that circICMT was significantly upregulated in bladder cancer tissue specimens. Overexpression of circICMT can inhibit cell migration, proliferation and colony formation ability, while knockdown of circICMT promotes the malignant phenotype of bladder cancer cells. Bioinformatics predictions have found that circICMT can bind to a variety of miRNAs and RBPs and may form a complex regulatory network to regulate the progression of bladder cancer.

CONCLUSION

circICMT is significantly highly expressed in bladder cancer, and intervening circICMT expression affects the malignant phenotype of bladder cancer cells in vivo and in vitro, which may provide potential biomarkers and therapeutic targets for the management of bladder cancer.

摘要

背景

环状RNA(circRNA)是一种新型的内源性单链RNA,具有共价闭合的环状结构。越来越多的证据表明,circRNA在肿瘤基因表达调控中发挥着重要作用。circICMT是由ICMT基因产生的环状RNA。目前,circICMT在膀胱癌中的分子功能尚不清楚。

方法

从RNA测序数据中鉴定差异表达的circRNA,并将circICMT鉴定为一种新的候选circRNA。采用qRT-PCR和桑格测序法检测circICMT在膀胱癌组织标本中的表达。构建过表达和敲低circICMT的稳定细胞系,以探讨circICMT对膀胱癌细胞的影响。通过伤口愈合实验、集落形成实验、CCK-8实验和异种肿瘤发生实验检测其生物学效应。

结果

本研究发现circICMT在膀胱癌组织标本中显著上调。circICMT的过表达可抑制细胞迁移、增殖和集落形成能力,而circICMT的敲低则促进膀胱癌细胞的恶性表型。生物信息学预测发现,circICMT可以与多种miRNA和RBP结合,并可能形成复杂的调控网络来调节膀胱癌的进展。

结论

circICMT在膀胱癌中显著高表达,干预circICMT的表达会影响膀胱癌细胞在体内和体外的恶性表型,这可能为膀胱癌的治疗提供潜在的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/178c0622f34e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/5fdea40795d8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/14f19f7093bf/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/58c4034a8f47/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/741d98fa4c2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/178c0622f34e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/5fdea40795d8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/14f19f7093bf/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/58c4034a8f47/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/741d98fa4c2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e72/11743880/178c0622f34e/gr5.jpg

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本文引用的文献

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Exploration of a Novel ICMT Inhibitor with More Solubility than Cysmethynil against Membrane Localization of KRAS Mutant in Colorectal Cancer.
探索一种新型 ICMT 抑制剂,与 Cysmethynil 相比,该抑制剂对结直肠癌 KRAS 突变体的膜定位具有更高的溶解性。
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LARP4B promotes hepatocellular carcinoma progression and impairs sorafenib efficacy by activating SPINK1-mediated EGFR pathway.LARP4B通过激活SPINK1介导的EGFR通路促进肝细胞癌进展并削弱索拉非尼疗效。
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Isoprenylcysteine carboxyl methyltransferase (ICMT) promotes invadopodia formation and metastasis in cancer cells.异戊烯半胱氨酸羧基甲基转移酶 (ICMT) 促进癌细胞中的侵袭伪足形成和转移。
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