• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

长链非编码RNA-CCDC144NL反义RNA1通过海绵吸附miR-940诱导WDR5表达促进肝细胞癌发展

LncRNA-CCDC144NL-AS1 Promotes the Development of Hepatocellular Carcinoma by Inducing WDR5 Expression via Sponging miR-940.

作者信息

Zhang Yingying, Zhang Hongyu, Wu Shuhuan

机构信息

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.

出版信息

J Hepatocell Carcinoma. 2021 May 3;8:333-348. doi: 10.2147/JHC.S306484. eCollection 2021.

DOI:10.2147/JHC.S306484
PMID:33977095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8104990/
Abstract

PURPOSE

This work was initiated to offer solid evidence regarding the expression and roles of long noncoding RNA (lncRNA) CCDC144NL-AS1 in hepatocellular carcinoma (HCC).

PATIENTS AND METHODS

Cell Counting Kit-8 assay, flow cytometric analysis, and invasion assays were used to explore the malignant biological characteristics of cells. Immunohistochemistry (IHC), Western blotting analysis, and real-time quantitative PCR (RT-qPCR) were used to analyze the expression level of related proteins and nucleic acids. Bl6/Rag2/GammaC double knockout mice were used for HCC modeling to address the therapeutic value of CCDC144NL-AS1.

RESULTS

CCDC144NL-AS1 was significantly upregulated in HCC tissue and had a marked relationship with the 5-year prognosis. In vitro study revealed that CCDC144NL-AS1 was highly expressed in HCC cell line MHCC97H but lowly expressed in normal hepatic cell line L02. Overexpression of CCDC144NL-AS1 in L02 enhanced the invasion and proliferation abilities of cells but inhibited the apoptosis rate. Knockdown of CCDC144NL-AS1 in MHCC97H weakened the invasion and proliferation abilities of cells but increased the apoptosis rate. CCDC144NL-AS1 was found to sponge miR-940 to induce the expression of WD repeat domain 5 (WDR5). ChIP-seq analysis identified that matrix metalloproteinase (MMP) 2, MMP9, and cyclin-dependent kinase (CDK) 1, CDK2, and CDK4 were all targets of WDR5. The recruitment of WDR5 to the promoter of these target genes upregulated the histone H3 lysine 4 trimethylation (H3K4me3) level in these regions and further induced the transcription of MMP2, MMP9, CDK1, CDK2, and CDK4. In vivo study revealed that compared to the normal liver tissue, CCDC144NL-AS1, WDR5, MMP2, MMP9, CDK1, CDK2, and CDK4 were all significantly upregulated in HCC tissue from the same mouse, while miR-940 was decreased. Besides, knockdown of CCDC144NL-AS1 or WDR5 or overexpression of miR-940 could all inhibit tumor growth.

CONCLUSION

CCDC144NL-AS1 drives HCC development by inducing MMP2/MMP9 and CDK1/CDK2/CDK4 expressions through miR-940/WDR5-regulated epigenetic pathway.

摘要

目的

开展本研究以提供关于长链非编码RNA（lncRNA）CCDC144NL-AS1在肝细胞癌（HCC）中的表达及作用的确凿证据。

患者与方法

采用细胞计数试剂盒-8检测、流式细胞术分析及侵袭实验来探究细胞的恶性生物学特性。运用免疫组织化学（IHC）、蛋白质免疫印迹分析及实时定量聚合酶链反应（RT-qPCR）来分析相关蛋白质和核酸的表达水平。利用Bl6/Rag2/γC双敲除小鼠建立HCC模型，以探讨CCDC144NL-AS1的治疗价值。

结果

CCDC144NL-AS1在HCC组织中显著上调，且与5年预后显著相关。体外研究显示，CCDC144NL-AS1在HCC细胞系MHCC97H中高表达，而在正常肝细胞系L-02中低表达。在L-02中过表达CCDC144NL-AS1可增强细胞的侵袭和增殖能力，但抑制细胞凋亡率。在MHCC97H中敲低CCDC144NL-AS1可削弱细胞的侵袭和增殖能力，但增加细胞凋亡率。发现CCDC144NL-AS1可吸附miR-940以诱导WD重复结构域5（WDR5）表达。染色质免疫沉淀测序（ChIP-seq）分析确定基质金属蛋白酶（MMP）2、MMP9以及细胞周期蛋白依赖性激酶（CDK）1、CDK2和CDK4均为WDR5的靶标。WDR5募集至这些靶基因的启动子可上调这些区域的组蛋白H3赖氨酸4三甲基化（H3K4me3）水平，并进一步诱导MMP2、MMP9、CDK1、CDK2和CDK4的转录。体内研究显示，与正常肝组织相比，同一小鼠的HCC组织中CCDC144NL-AS1、WDR5、MMP2、MMP9、CDK1、CDK2和CDK4均显著上调，而miR-940则降低。此外，敲低CCDC144NL-AS1或WDR5或过表达miR-940均可抑制肿瘤生长。

结论

CCDC144NL-AS1通过miR-940/WDR5调控的表观遗传途径诱导MMP2/MMP9和CDK1/CDK2/CDK4表达，从而推动HCC发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/8803712aa2fc/JHC-8-333-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/a3160a55fd45/JHC-8-333-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/c209d67bd463/JHC-8-333-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/428c10d40433/JHC-8-333-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/e74fc120c29a/JHC-8-333-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/d7ec1d000e87/JHC-8-333-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/d149e10d9312/JHC-8-333-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/62dbd6df3f3d/JHC-8-333-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/3dfd6907eb79/JHC-8-333-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/8803712aa2fc/JHC-8-333-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/a3160a55fd45/JHC-8-333-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/c209d67bd463/JHC-8-333-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/428c10d40433/JHC-8-333-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/e74fc120c29a/JHC-8-333-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/d7ec1d000e87/JHC-8-333-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/d149e10d9312/JHC-8-333-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/62dbd6df3f3d/JHC-8-333-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/3dfd6907eb79/JHC-8-333-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ee/8104990/8803712aa2fc/JHC-8-333-g0009.jpg

相似文献

1
LncRNA-CCDC144NL-AS1 Promotes the Development of Hepatocellular Carcinoma by Inducing WDR5 Expression via Sponging miR-940.长链非编码RNA-CCDC144NL反义RNA1通过海绵吸附miR-940诱导WDR5表达促进肝细胞癌发展
J Hepatocell Carcinoma. 2021 May 3;8:333-348. doi: 10.2147/JHC.S306484. eCollection 2021.
2
Long Noncoding RNA CCDC144NL-AS1 Promotes the Oncogenicity of Osteosarcoma by Acting as a Molecular Sponge for microRNA-490-3p and Thereby Increasing HMGA2 Expression.长链非编码RNA CCDC144NL-AS1通过作为微小RNA-490-3p的分子海绵发挥作用，从而增加HMGA2表达，促进骨肉瘤的致癌性。
Onco Targets Ther. 2021 Jan 6;14:1-13. doi: 10.2147/OTT.S280912. eCollection 2021.
3
Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2.长链非编码 RNA UPK1A-AS1 提示肝细胞癌预后不良，并通过与 EZH2 相互作用促进细胞增殖。
J Exp Clin Cancer Res. 2020 Oct 29;39(1):229. doi: 10.1186/s13046-020-01748-y.
4
LncRNA CCDC144NL-AS1 Serves as a Prognosis Biomarker for Non-small Cell Lung Cancer and Promotes Cellular Function by Targeting miR-490-3p.长链非编码RNA CCDC144NL-AS1作为非小细胞肺癌的预后生物标志物并通过靶向miR-490-3p促进细胞功能。
Mol Biotechnol. 2021 Oct;63(10):933-940. doi: 10.1007/s12033-021-00351-6. Epub 2021 Jun 11.
5
Long non-coding RNA CCDC144NL-AS1 promotes cell proliferation by regulating the miR-363-3p/GALNT7 axis in colorectal cancer.长链非编码RNA CCDC144NL-AS1通过调控miR-363-3p/GALNT7轴促进结直肠癌细胞增殖。
J Cancer. 2022 Jan 1;13(3):752-763. doi: 10.7150/jca.65885. eCollection 2022.
6
Long noncoding RNA CCDC144NL-AS1 knockdown induces naïve-like state conversion of human pluripotent stem cells.长链非编码 RNA CCDC144NL-AS1 敲低诱导人多能干细胞向原始态样转换。
Stem Cell Res Ther. 2019 Jul 29;10(1):220. doi: 10.1186/s13287-019-1323-9.
7
Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer.长链非编码 RNA CCDC144NL-AS1 通过作为竞争性内源性 RNA 吸附 miR-143-3p 并调控 MAP3K7 来调节胃癌。
Cell Death Dis. 2020 Jul 9;11(7):521. doi: 10.1038/s41419-020-02740-2.
8
Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma.长链非编码 RNA ZFPM2-AS1 通过调控 miR-139/GDF10 促进肝癌细胞侵袭。
J Exp Clin Cancer Res. 2020 Aug 14;39(1):159. doi: 10.1186/s13046-020-01664-1.
9
LncRNA DARS-AS1 aggravates the growth and metastasis of hepatocellular carcinoma via regulating the miR-3200-5p-Cytoskeleton associated protein 2 (CKAP2) axis.长链非编码 RNA DARS-AS1 通过调控 miR-3200-5p-细胞骨架相关蛋白 2（CKAP2）轴促进肝癌的生长和转移。
Bioengineered. 2021 Dec;12(1):8217-8232. doi: 10.1080/21655979.2021.1982272.
10
LncRNA TMPO-AS1 promotes hepatocellular carcinoma cell proliferation, migration and invasion through sponging miR-329-3p to stimulate FOXK1-mediated AKT/mTOR signaling pathway.长链非编码 RNA TMPO-AS1 通过海绵吸附 miR-329-3p 来刺激 FOXK1 介导的 AKT/mTOR 信号通路，从而促进肝癌细胞的增殖、迁移和侵袭。
Cancer Med. 2020 Jul;9(14):5235-5246. doi: 10.1002/cam4.3046. Epub 2020 May 27.

引用本文的文献

1
The value of acetylation reader YEATS2 in hepatocellular carcinoma management.乙酰化阅读器YEATS2在肝细胞癌治疗中的价值
Sci Rep. 2025 Jul 29;15(1):27613. doi: 10.1038/s41598-025-09945-5.
2
HBV core protein enhances WDR46 stabilization to upregulate NUSAP1 and promote HCC progression.乙肝病毒核心蛋白增强WDR46稳定性以上调NUSAP1并促进肝癌进展。
Hepatol Commun. 2025 May 6;9(5). doi: 10.1097/HC9.0000000000000680. eCollection 2025 May 1.
3
The role of long non-coding RNA in hepatocellular carcinoma.长链非编码 RNA 在肝细胞癌中的作用。

本文引用的文献

1
Long Noncoding RNA CCDC144NL-AS1 Promotes the Oncogenicity of Osteosarcoma by Acting as a Molecular Sponge for microRNA-490-3p and Thereby Increasing HMGA2 Expression.长链非编码RNA CCDC144NL-AS1通过作为微小RNA-490-3p的分子海绵发挥作用，从而增加HMGA2表达，促进骨肉瘤的致癌性。
Onco Targets Ther. 2021 Jan 6;14:1-13. doi: 10.2147/OTT.S280912. eCollection 2021.
2
BPA modulates the WDR5/TET2 complex to regulate ERβ expression in eutopic endometrium and drives the development of endometriosis.BPA 通过调节 WDR5/TET2 复合物来调节在位子宫内膜中 ERβ 的表达，并驱动子宫内膜异位症的发展。
Environ Pollut. 2021 Jan 1;268(Pt B):115748. doi: 10.1016/j.envpol.2020.115748. Epub 2020 Sep 28.
3
Aging (Albany NY). 2024 Feb 8;16(4):4052-4073. doi: 10.18632/aging.205523.
4
Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition.ncRNAs 通过调控细胞周期影响 CDK4/6 抑制的效率。
Int J Mol Sci. 2023 May 18;24(10):8939. doi: 10.3390/ijms24108939.
5
Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer.焦亡相关长链非编码RNA：一种新型的结直肠癌预后标志物
Front Oncol. 2022 Nov 30;12:983895. doi: 10.3389/fonc.2022.983895. eCollection 2022.
6
The mechanism of lncRNAs in the crosstalk between epithelial-mesenchymal transition and tumor microenvironment for early colon adenocarcinoma based on molecular subtyping.基于分子亚型的lncRNAs在上皮-间质转化与早期结肠腺癌肿瘤微环境相互作用中的机制
Front Genet. 2022 Nov 16;13:997739. doi: 10.3389/fgene.2022.997739. eCollection 2022.
7
A review on the role of cyclin dependent kinases in cancers.细胞周期蛋白依赖性激酶在癌症中的作用综述。
Cancer Cell Int. 2022 Oct 20;22(1):325. doi: 10.1186/s12935-022-02747-z.
8
Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI.基于 MRI 的脑白质高信号的表观遗传学和综合组学分析。
Brain. 2023 Feb 13;146(2):492-506. doi: 10.1093/brain/awac290.
9
LncRNA00978 contributes to growth and metastasis of hepatocellular carcinoma cells via mediating microRNA-125b-5p/SOX12 pathway.LncRNA00978 通过介导 microRNA-125b-5p/SOX12 通路促进肝癌细胞的生长和转移。
Bioengineered. 2022 Apr;13(4):11228-11239. doi: 10.1080/21655979.2022.2063648.
10
A New Strategy to Identify ceRNA-Based CCDC144NL-AS1/SERPINE1 Regulatory Axis as a Novel Prognostic Biomarker for Stomach Adenocarcinoma High Throughput Transcriptome Data Mining and Computational Verification.一种基于ceRNA的CCDC144NL-AS1/SERPINE1调控轴作为胃腺癌新的预后生物标志物的鉴定新策略：高通量转录组数据挖掘与计算验证
Front Oncol. 2022 Jan 27;11:802727. doi: 10.3389/fonc.2021.802727. eCollection 2021.
Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer.
长链非编码 RNA CCDC144NL-AS1 通过作为竞争性内源性 RNA 吸附 miR-143-3p 并调控 MAP3K7 来调节胃癌。
Cell Death Dis. 2020 Jul 9;11(7):521. doi: 10.1038/s41419-020-02740-2.
4
miR-223 overexpression inhibits doxorubicin-induced autophagy by targeting FOXO3a and reverses chemoresistance in hepatocellular carcinoma cells.miR-223 过表达通过靶向 FOXO3a 抑制阿霉素诱导的自噬，逆转肝癌细胞的化疗耐药性。
Cell Death Dis. 2019 Nov 6;10(11):843. doi: 10.1038/s41419-019-2053-8.
5
Histone Deacetylase Expressions in Hepatocellular Carcinoma and Functional Effects of Histone Deacetylase Inhibitors on Liver Cancer Cells In Vitro.组蛋白去乙酰化酶在肝细胞癌中的表达及组蛋白去乙酰化酶抑制剂对肝癌细胞的体外功能影响
Cancers (Basel). 2019 Oct 18;11(10):1587. doi: 10.3390/cancers11101587.
6
Role of miRNA sponges in hepatocellular carcinoma.miRNA 海绵在肝细胞癌中的作用。
Clin Chim Acta. 2020 Jan;500:10-19. doi: 10.1016/j.cca.2019.09.013. Epub 2019 Oct 8.
7
Mechanisms and importance of histone modification enzymes in targeted therapy for hepatobiliary cancers.组蛋白修饰酶在肝胆癌靶向治疗中的机制及重要性
Discov Med. 2019 Jul;28(151):17-28.
8
Expression of HDAC4 in Stage B Hepatocellular Carcinoma and Its Influence on Survival.HDAC4在B期肝细胞癌中的表达及其对生存的影响。
Ann Clin Lab Sci. 2019 Mar;49(2):189-192.
9
Unmasking the pathological and therapeutic potential of histone deacetylases for liver cancer.揭示组蛋白去乙酰化酶在肝癌中的病理和治疗潜力。
Expert Rev Gastroenterol Hepatol. 2019 Mar;13(3):247-256. doi: 10.1080/17474124.2019.1568870. Epub 2019 Jan 29.
10
Loss of HDAC3 results in nonreceptive endometrium and female infertility.HDAC3 的缺失导致子宫内膜容受性丧失和女性不孕。
Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aaf7533.