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长链非编码 RNA Lnc-LALC 通过表观遗传沉默 LZTS1 促进结直肠癌肝转移。

Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1.

机构信息

The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, PR China.

Department of General Surgery, The First affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.

出版信息

Cell Death Dis. 2021 Feb 26;12(2):224. doi: 10.1038/s41419-021-03461-w.

DOI:10.1038/s41419-021-03461-w
PMID:33637680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7910484/
Abstract

Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.

摘要

结直肠癌（CRC）是全世界最常见的癌症之一，严重危害人类健康。肝转移是影响 CRC 长期预后的重要因素，而 CRLM（结直肠癌伴肝转移）的确切机制尚未完全阐明。LZTS1 在许多癌症中被发现失调，尤其是在 CRC 中。有理论认为，LZTS1 启动子区域的异常高甲基化导致了多种恶性肿瘤中 LZTS1 的异常表达。尽管已经报道了 LZTS1 在 CRC 细胞增殖中的作用，但它在 CRLM 中的作用尚不清楚。许多研究报告称，长链非编码 RNA（lncRNA）可以通过调节许多肿瘤中的基因甲基化状态来调节基因表达水平。然而，在 CRLM 中是否存在 lncRNA 可以改变 LZTS1 的甲基化状态尚不清楚。在这项研究中，我们旨在研究是否有 lncRNA 可以通过影响 DNA 甲基化来调节 CRLM 中 LZTS1 的表达。我们发现，CRC 中上调的 Lnc-LALC 与 LZTS1 表达呈负相关，并且 Lnc-LALC 可以在我们的研究中调节 LZTS1 在 mRNA 和蛋白质水平上的表达。功能上，Lnc-LALC 通过抑制 LZTS1 的表达增强了 CRC 细胞在体外和体内的转移能力。此外，精确机制探索表明，lnc-LALC 可以通过与 Enhancer of zeste homolog 2（EZH2）结合，招募 DNA 甲基转移酶（DNMTs）到 LZTS1 启动子上，然后通过 DNMTs 介导的 DNA 甲基化改变 LZTS1 的表达。总之，我们的数据表明 Lnc-LALC/LZTS1 轴在 CRLM 发展中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfd/7910484/dc549c6606cb/41419_2021_3461_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cfd/7910484/dc549c6606cb/41419_2021_3461_Fig7_HTML.jpg
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本文引用的文献

1
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Cancer Manag Res. 2020 Aug 21;12:7539-7552. doi: 10.2147/CMAR.S267665. eCollection 2020.
2
LINC00922 Accelerates the Proliferation, Migration and Invasion of Lung Cancer Via the miRNA-204/CXCR4 Axis.LINC00922 通过 miRNA-204/CXCR4 轴促进肺癌的增殖、迁移和侵袭。
Med Sci Monit. 2019 Jul 9;25:5075-5086. doi: 10.12659/MSM.916327.
3
Is an Epigenetically Regulated Tumor Suppressor Essential for Activation of the DNA Damage Response.
TRIM38通过增强CCT6A泛素化抑制MYC途径来抑制结直肠癌进展。
Adv Sci (Weinh). 2025 Apr;12(16):e2411285. doi: 10.1002/advs.202411285. Epub 2025 Mar 6.
4
Examination of the effects of capecitabine treatment on the HT-29 colorectal cancer cell line and HCG 11, HCG 15, and HCG 18 lncRNAs in CRC patients before and after chemotherapy.考察卡培他滨治疗对CRC患者化疗前后HT-29结肠癌细胞系以及HCG 11、HCG 15和HCG 18长链非编码RNA的影响。
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun;398(6):6929-6940. doi: 10.1007/s00210-024-03674-8. Epub 2024 Dec 19.
5
LINC00161 upregulated by M2-like tumor-associated macrophages promotes hepatocellular carcinoma progression by methylating HACE1 promoters.由M2样肿瘤相关巨噬细胞上调的LINC00161通过甲基化HACE1启动子促进肝细胞癌进展。
Cytotechnology. 2024 Dec;76(6):777-793. doi: 10.1007/s10616-024-00653-y. Epub 2024 Aug 16.
6
The epigenetic landscape in intestinal stem cells and its deregulation in colorectal cancer.肠干细胞中的表观遗传学景观及其在结直肠癌中的失调。
Stem Cells. 2024 Jun 14;42(6):509-525. doi: 10.1093/stmcls/sxae027.
7
Bone marrow mesenchymal stem cell-derived exosomes promote osteoblast proliferation, migration and inhibit apoptosis by regulating KLF3-AS1/miR-338-3p.骨髓间充质干细胞来源的外泌体通过调节 KLF3-AS1/miR-338-3p 促进成骨细胞增殖、迁移和抑制凋亡。
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一个受表观遗传调控的肿瘤抑制因子对于 DNA 损伤反应的激活是必不可少的。
Cancer Res. 2019 Jun 15;79(12):3050-3062. doi: 10.1158/0008-5472.CAN-18-2034. Epub 2019 Feb 22.
4
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6
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7
Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1.斯特拉通过防止 DNMT1 介导的从头甲基化来保护卵母细胞的甲基组。
Nature. 2018 Dec;564(7734):136-140. doi: 10.1038/s41586-018-0751-5. Epub 2018 Nov 28.
8
Epigenome-based cancer risk prediction: rationale, opportunities and challenges.基于表观基因组的癌症风险预测：原理、机遇与挑战。
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9
Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's esophagus.识别用于 Barrett 食管非内镜检测的 DNA 甲基化生物标志物。
Sci Transl Med. 2018 Jan 17;10(424). doi: 10.1126/scitranslmed.aao5848.
10
Cancer statistics, 2018.癌症统计数据，2018 年。
CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.