■以前,据报道,长链非编码RNA(lncRNA)基因AP001469.3参与了免疫相关lncRNA签名的构建,在结直肠癌(CRC)患者中显示出有希望的临床预测价值。然而,AP001469.3在CRC中的临床和免疫学意义和生物学功能尚不清楚.在这项研究中,我们旨在探讨AP001469.3在CRC进展中的作用,从而为CRC治疗开辟了一条途径。
■我们的研究从癌症基因组图谱(TCGA)数据库收集数据,并通过生物信息学分析研究AP001469.3在CRC中的作用。通过估计已知RNA转录物的相对子集(CIBERSORT)的细胞类型鉴定和使用表达数据(ESTIMATE)方法估计MAlignant肿瘤组织中的STromal和免疫细胞评估免疫浸润。通过体外实验验证了AP001469.3在CRC中的生物学功能。使用基因集富集分析(GSEA)来估计功能途径和基因签名的富集。
■在这项工作中,在CRC中发现AP001469.3的高表达,并且与CRC的肿瘤淋巴结转移(TNM)分期呈正相关.结肠腺癌(COAD)中AP001469.3的表达与微卫星不稳定性(MSI)密切相关。此外,AP001469.3表达与StromalScore相关,ImmuneScore,估计,CRC中免疫细胞浸润(ICI)水平和免疫检查点(ICP)基因表达。随后的结果表明,使用免疫表型(IPS),免疫疗法在AP001469.3低表达的CRC患者中可能更有效。我们证实AP001469.3基因ENST00000430259的转录本在CRC组织和细胞系中高表达。体外实验表明,ENST00000430259敲低降低了细胞增殖,CRC细胞的迁移和侵袭。最后,我们的GSEA结果显示高和低AP001469.3表达组之间的大多数差异富集的信号通路是免疫相关的。
■放在一起,我们的研究表明,lncRNA基因AP001469.3与CRC的免疫学特征相关,并促进CRC的恶性进展.此外,AP001469.3可作为CRC患者的免疫治疗指标和治疗靶点。
UNASSIGNED: Previously, long non-coding RNA (lncRNA) gene AP001469.3 was reported to participate in the construction of an immune-related lncRNA signature, which showed promising clinical predictive value in colorectal cancer (CRC) patients. However, the clinical and immunological significance and biological function of AP001469.3 in CRC remain unclear. In this study, we aim to explore the roles of AP001469.3 in CRC progression, thereby opening an avenue for CRC treatment.
UNASSIGNED: Our study collected data from The Cancer Genome Atlas (TCGA) database and investigated the role of AP001469.3 in CRC through bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods evaluated the immune infiltration. The biological functions of AP001469.3 in CRC were validated by in vitro experiments. Gene set enrichment analysis (GSEA) was used to estimate the enrichment of functional pathways and gene signatures.
UNASSIGNED: In this work, high expression of AP001469.3 was found in CRC and was positively associated with tumor-node-metastasis (TNM) stage in CRC. AP001469.3 expression had a strong relationship with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Additionally, AP001469.3 expression was associated with StromalScore, ImmuneScore, ESTIMATEScore, immune cell infiltration (ICI) levels and immune checkpoint (ICP) genes expression in CRC. Subsequent results showed that immunotherapy could be more effective in CRC patients with low-AP001469.3 expression using the immunophenoscore (IPS). We confirmed that the transcript of AP001469.3 gene ENST00000430259 was highly expressed in CRC tissues and cell lines. In vitro experiments indicated that ENST00000430259 knockdown reduced the proliferation, migration and invasion of CRC cells. Finally, our GSEA results showed that the majority of the differentially enriched signaling pathways between the high- and low-AP001469.3 expression groups were immune-related.
UNASSIGNED: Taken together, our study demonstrates that lncRNA gene AP001469.3 is associated with immunological characteristics in CRC and promotes malignant progression of CRC. Moreover, AP001469.3 can be potentially used as an immunotherapeutic indicator and a therapeutic target for CRC patients.