LINC00955 suppresses colorectal cancer growth by acting as a molecular scaffold of TRIM25 and Sp1 to Inhibit DNMT3B-mediated methylation of the PHIP promoter
文献类型：期刊论文
| 作者 | Ren, Ganglin3,4; Li, Hongyan4; Hong, Dan4; Hu, Fangyu4; Jin, Rongjia4; Wu, Shuang4; Sun, Wenhao4; Jin, Honglei4; Zhao, Lingling4; Zhang, Xiaodong2 |
| 刊名 | BMC CANCER
 |
| 出版日期 | 2023-09-23 |
| 卷号 | 23期号:1页码:20 |
| 关键词 | LINC00955 Colorectal cancer Cell cycle CDK2 PHIP Sp1 |
| DOI | 10.1186/s12885-023-11403-2 |
| 通讯作者 | Liu, Dongxiang(dxl@mail.shcnc.ac.cn) ; Huang, Chuanshu(huangchuanshu@hotmail.com) ; Huang, Haishan(haishan_333@163.com) |
| 英文摘要 | BackgroundLong non-coding RNAs play an important role in the development of colorectal cancer (CRC), while many CRC-related lncRNAs have not yet been identified.MethodsThe relationship between the expression of LINC00955 (Long Intergenic Non-protein Coding RNA 955) and the prognosis of colorectal cancer patients was analyzed using the sequencing results of the TCGA database. LINC00955 expression levels were measured using qRT-PCR. The anti-proliferative activity of LINC00955 was evaluated using CRC cell lines in vitro and xenograft models in nude mice in vivo. The interaction of TRIM25-Sp1-DNMT3B-PHIP-CDK2 was analyzed by western blotting, protein degradation experiment, luciferase, RNA-IP, RNA pull-down assays and immunohistochemically analysis. The biological roles of LINC00955, tripartite motif containing 25 (TRIM25), Sp1 transcription factor (Sp1), DNA methyltransferase 3 beta (DNMT3B), pleckstrin homology domain interacting protein (PHIP), cyclin dependent kinase 2 (CDK2) in colorectal cancer cells were analyzed using ATP assays, Soft agar experiments and EdU assays.ResultsThe present study showed that LINC00955 is downregulated in CRC tissues, and such downregulation is associated with poor prognosis of CRC patients. We found that LINC00955 can inhibit CRC cell growth both in vitro and in vivo. Evaluation of its mechanism of action showed that LINC00955 acts as a scaffold molecule that directly promotes the binding of TRIM25 to Sp1, and promotes ubiquitination and degradation of Sp1, thereby attenuating transcription and expression of DNMT3B. DNMT3B inhibition results in hypomethylation of the PHIP promoter, in turn increasing PHIP transcription and promoting ubiquitination and degradation of CDK2, ultimately leading to G0/G1 growth arrest and inhibition of CRC cell growth.ConclusionsThese findings indicate that downregulation of LINC00955 in CRC cells promotes tumor growth through the TRIM25/Sp1/DNMT3B/PHIP/CDK2 regulatory axis, suggesting that LINC00955 may be a potential target for the therapy of CRC. |
| WOS关键词 | LONG NONCODING RNAS ; DNA METHYLATION ; CELL-CYCLE ; TRANSCRIPTIONAL REGULATION ; DNMT3B ; PHOSPHORYLATION ; TRANSFORMATION ; PROLIFERATION ; PROTEINS ; TARGETS |
| 资助项目 | Wenzhou Science and Technology Bureau[Y20190061] ; Key Discipline of Zhejiang Province in Medical Technology of Zhejiang Province[2013TD10] ; Key Project of the Science and Technology Innovation Team of Zhejiang Province[2013TD10] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | BMC |
| WOS记录号 | WOS:001075729700003 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307348]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Liu, Dongxiang; Huang, Chuanshu; Huang, Haishan |
| 作者单位 | 1.Chinese Acad Sci, Ctr Chem Biol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China 3.Jiaxing Ctr Dis Control & Prevent, Jiaxing 314050, Zhejiang, Peoples R China 4.Wenzhou Med Univ, Sch Lab Med & Life Sci, Zhejiang Prov Key Lab Med Genet, Key Lab Lab Med,Minist Educ, Wenzhou, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ren, Ganglin,Li, Hongyan,Hong, Dan,et al. LINC00955 suppresses colorectal cancer growth by acting as a molecular scaffold of TRIM25 and Sp1 to Inhibit DNMT3B-mediated methylation of the PHIP promoter[J]. BMC CANCER,2023,23(1):20. |
| APA | Ren, Ganglin.,Li, Hongyan.,Hong, Dan.,Hu, Fangyu.,Jin, Rongjia.,...&Huang, Haishan.(2023).LINC00955 suppresses colorectal cancer growth by acting as a molecular scaffold of TRIM25 and Sp1 to Inhibit DNMT3B-mediated methylation of the PHIP promoter.BMC CANCER,23(1),20. |
| MLA | Ren, Ganglin,et al."LINC00955 suppresses colorectal cancer growth by acting as a molecular scaffold of TRIM25 and Sp1 to Inhibit DNMT3B-mediated methylation of the PHIP promoter".BMC CANCER 23.1(2023):20. |
入库方式： OAI收割
来源：上海药物研究所
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