长非编码RNA在结直肠癌（CRC）的发育中起着重要作用，而许多与CRC相关的长lncRNA尚未被鉴定出来。本研究使用TCGA数据库的测序结果分析了LINC00955（长间隔非蛋白编码RNA 955）的表达与CRC患者预后之间的关系。使用qRT-PCR测量了LINC00955表达水平。利用体外的CRC细胞系和体内裸鼠异种移植模型评估了LINC00955的抗增殖活性。通过西方印迹、蛋白降解实验、荧光素酶、RNA-IP、RNA pull-down实验和免疫组化分析，分析了TRIM25-Sp1-DNMT3B-PHIP-CDK2的相互作用。利用ATP测定、软琼脂实验和EdU实验分析了LINC00955、三部位结构域含有25（TRIM25）、Sp1转录因子（Sp1）、DNA甲基转移酶3 beta（DNMT3B）、pleckstrin单P结构域相互作用蛋白（PHIP）、细胞周期蛋白依赖激酶2（CDK2）在结直肠癌细胞中的生物学作用。本研究显示LINC00955在CRC组织中下调，并且这种下调与CRC患者预后不良相关。我们发现LINC00955可以在体内外抑制CRC细胞生长。其作用机制研究表明，LINC00955充当了一个直接促进TRIM25与Sp1结合的支架分子，并促进Sp1泛素化和降解，从而抑制DNMT3B的转录和表达。DNMT3B的抑制导致PHIP启动子下甲基化，进而增加PHIP的转录，促进CDK2的泛素化和降解，最终导致G0/G1期增殖阻滞和抑制CRC细胞生长。这些发现表明LINC00955在CRC细胞中的下调通过TRIM25/Sp1/DNMT3B/PHIP/CDK2调控轴促进肿瘤生长，提示LINC00955可能是CRC治疗的一个潜在靶点。（C）2023 BioMed Central有限公司，Springer自然出版集团的合作伙伴。

Long non-coding RNAs play an important role in the development of colorectal cancer (CRC), while many CRC-related lncRNAs have not yet been identified.The 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.The 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.These 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.© 2023. BioMed Central Ltd., part of Springer Nature.