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ZMAT2 凝聚物调节 TRIM28 的可变剪接，减少细胞内 ROS 积累，从而促进 HCC 细胞的增殖。

ZMAT2 condensates regulate the alternative splicing of TRIM28 to reduce cellular ROS accumulation, thereby promoting the proliferation of HCC cells.

机构信息

Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Postdoctoral Station of Medical Aspects of Specific Environments, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Cell Commun Signal. 2024 Aug 20;22(1):407. doi: 10.1186/s12964-024-01790-9.

DOI:10.1186/s12964-024-01790-9
PMID:39164737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11337747/
Abstract

Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

摘要

剪接因子表达失调在肝细胞癌（HCC）的进展中起着关键作用。我们的研究发现，剪接因子 ZMAT2 在 HCC 中的表达水平增加，促进了 HCC 细胞的增殖。RNAseq 数据表明，ZMAT2 的缺失导致 mRNA 外显子跳过，而 RIPseq 数据进一步揭示了 ZMAT2 的 mRNA 结合基序。对 RNAseq 和 RIPseq 数据的综合分析表明，ZMAT2 在 TRIM28 mRNA 的成熟过程中起着关键作用。敲低 ZMAT2 导致 TRIM28 第 11 外显子的 25 个碱基缺失，最终导致无意义介导的衰变（NMD）。我们的数据表明，ZMAT2 可以调节 TRIM28 以减少 HCC 细胞中 ROS 的积累，从而促进其增殖。我们的研究还发现，ZMAT2 能够发生相分离，导致 HCC 细胞内形成液滴凝聚物。此外，还发现 ZMAT2 能够与 TRIM28 mRNA 形成蛋白-核酸凝聚物。总之，这项研究首次揭示了 ZMAT2 和 TRIM28 mRNA 形成蛋白-核酸凝聚物，从而调节 TRIM28 mRNA 的剪接。ZMAT2 在 HCC 中的高表达导致 TRIM28 表达上调和 ROS 积累减少，最终加速 HCC 细胞的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/260cd27b8660/12964_2024_1790_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/e33341aa4f82/12964_2024_1790_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/225ab280959a/12964_2024_1790_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/72a45a736d27/12964_2024_1790_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/260cd27b8660/12964_2024_1790_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/e33341aa4f82/12964_2024_1790_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/55d3925698c6/12964_2024_1790_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/4508e1b65aac/12964_2024_1790_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/ebac8855d184/12964_2024_1790_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/225ab280959a/12964_2024_1790_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/72a45a736d27/12964_2024_1790_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6319/11337747/260cd27b8660/12964_2024_1790_Fig9_HTML.jpg

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Br J Cancer. 2024 Jul;131(1):77-89. doi: 10.1038/s41416-024-02689-5. Epub 2024 May 25.
2
RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing.RBFOX2 失调通过选择性剪接促进胰腺癌的进展和转移。
Nat Commun. 2023 Dec 19;14(1):8444. doi: 10.1038/s41467-023-44126-w.
3
Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer.
癌发生、肿瘤进展和转移中的相分离：癌症标志的一瞥。
J Hematol Oncol. 2023 Dec 18;16(1):123. doi: 10.1186/s13045-023-01522-5.
4
Hypoxia induces hepatocellular carcinoma metastasis via the HIF-1α/METTL16/lnc-CSMD1-7/RBFOX2 axis.缺氧通过HIF-1α/METTL16/lnc-CSMD1-7/RBFOX2轴诱导肝细胞癌转移。
iScience. 2023 Nov 19;26(12):108495. doi: 10.1016/j.isci.2023.108495. eCollection 2023 Dec 15.
5
Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells.抑制无义介导的mRNA降解可降低人纤维肉瘤细胞的致瘤性。
NAR Cancer. 2023 Sep 6;5(3):zcad048. doi: 10.1093/narcan/zcad048. eCollection 2023 Sep.
6
Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration.无义介导的 mRNA 降解在神经元生理学和神经退行性变中的作用。
Trends Neurosci. 2023 Oct;46(10):879-892. doi: 10.1016/j.tins.2023.07.001. Epub 2023 Aug 3.
7
Pre-mRNA splicing-associated diseases and therapies.前体 mRNA 剪接相关疾病和治疗方法。
RNA Biol. 2023 Jan;20(1):525-538. doi: 10.1080/15476286.2023.2239601.
8
Ferroptosis in mitochondrial cardiomyopathy.铁死亡与线粒体心肌病。
Trends Cell Biol. 2024 Feb;34(2):150-160. doi: 10.1016/j.tcb.2023.06.002. Epub 2023 Jul 5.
9
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.缺氧微环境与癌症：分子机制与治疗干预。
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10
Targeting splicing factors for cancer therapy.针对剪接因子的癌症治疗。
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