背景:最近的研究强调了长链非编码RNA(lncRNA)在各种恶性肿瘤的发作和进展中的多功能功能。尽管如此,关于lnc-SOX9-4在结直肠癌(CRC)进展中的作用的知识不足.
方法:生物信息学分析用于鉴定新的lncRNA(lnc-SOX9-4),并且使用qRT-PCR验证了RNA在CRC中的表达模式。基因本体论(GO)术语分析和基因集富集分析(GSEA)用于鉴定lnc-SOX9-4的相关机制和作用。进行免疫浸润分析以评估lnc-SOX9-4如何与肿瘤免疫细胞浸润水平相关联。进行体外和体内表型分析以仔细检查lnc-SOX9-4如何影响CRC的增殖和转移。RNA下拉,质谱分析,荧光原位杂交(FISH),西方印迹,和RIP检测有助于验证与CRC进展相关的lnc-SOX9-4机制。
结果:在样品CRC细胞和组织中观察到lnc-SOX9-4的上调。lnc-SOX9-4水平升高与不良临床预后呈正相关。Lnc-SOX9-4与几种类型的免疫浸润细胞密切相关。功能上,lnc-SOX9-4的敲除显著抑制CRC细胞增殖,迁移,和入侵能力。机械上,YBX1被鉴定为lnc-SOX9-4,是细胞核中特异性相互作用的蛋白质。Lnc-SOX9-4可以通过抑制YBX1的聚泛素化和降解来稳定YBX1蛋白水平。此外,表型拯救实验表明,lnc-SOX9-4通过调节YBX1水平增强了CRC细胞增殖和转移的潜力。
结论:Lnc-SOX9-4通过抑制细胞质移位和促进YBX1蛋白水平促进CRC进展,可作为诊断和治疗CRC的新治疗靶点。
Recent research has highlighted the versatile functions of long non-coding RNAs (lncRNAs) in the onset and progression of various malignancies. Still, insufficient knowledge is available on how lnc-SOX9-4 functions in colorectal cancer (CRC) progression.
Bioinformatics analysis was used to identify a novel lncRNA (lnc-SOX9-4), and the expression pattern of the RNA in CRC was verified using qRT-PCR. Gene ontology (GO) term analysis and Gene set enrichment analysis (GSEA) were implemented for the identification of the related mechanisms and roles of lnc-SOX9-4. Immune infiltration analysis was conducted for assessment of how lnc-SOX9-4 is linked to tumor immune cell infiltration level. Both in vitro and in vivo phenotype analyses were conducted for scrutinizing how lnc-SOX9-4 impacts the proliferation and metastasis of CRC. RNA pulldown, mass spectrometry analysis, fluorescent in situ hybridization (FISH), western blotting, and RIP assay aided in verifying lnc-SOX9-4 mechanisms linked to CRC progression.
An upregulation of lnc-SOX9-4 was observed in the sample CRC cells and tissues. Elevated lnc-SOX9-4 levels showed a positive association with poor clinical prognosis. Lnc-SOX9-4 was closely correlated to several types of immune infiltrating cells. Functionally, the knockdown of lnc-SOX9-4 significantly inhibited CRC cell proliferation, migration, and invasion abilities. Mechanistically, YBX1 was identified as lnc-SOX9-4, specifically interacting protein in the nucleus. Lnc-SOX9-4 could stabilize YBX1 protein levels by inhibiting poly-ubiquitination and degradation of YBX1. Furthermore, phenotype rescue experiments reveal that lnc-SOX9-4 enhanced the CRC cellular potential to proliferate and metastasize by regulating YBX1 levels.
Lnc-SOX9-4 promoted CRC progression by suppressing cytoplasmic translocation and promoting protein levels of YBX1 can serve as novel treatment targets for diagnosing and treating CRC.