RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:LncRNA AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11/PI3K/AKT axis and is associated with patients prognosis.
LncRNA AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11/PI3K/AKT axis and is associated with patients prognosis.
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LncRNA是影响肿瘤发展的关键因素。本研究旨在探讨一种新型lncRNA对肝细胞癌(HCC)进展的影响。
使用limma和survival R包在癌症基因组图谱数据库中鉴定候选lncRNA。研究lncRNA AC099850.3对HCC细胞增殖、凋亡、迁移和侵袭的影响,及其与HCC中免疫细胞的关联。此外,阐明lncRNA AC099850.3在HCC中的功能机制。
在肿瘤组织中鉴定出lncRNA AC099850.3的异常表达,并确定了其在HCC中的预后相关性。结果显示,AC099850.3在HCC组织和细胞系中高表达,并预测HCC患者预后不良。此外,敲低AC099850.3显著抑制了HCC细胞的增殖和转移潜能,并促进了HCC细胞的凋亡。基因集富集分析结果显示,PI3K/AKT通路与AC099850.3的生物学功能相关,并通过western blotting进一步验证。PRR11被鉴定为AC099850.3的靶基因,我们确定AC099850.3在PRR11/PI3K/AKT轴中作为癌基因发挥作用。免疫细胞浸润分析结果显示,AC099850.3与T滤泡辅助细胞、M0巨噬细胞、CD4+记忆T细胞和记忆B细胞呈正相关。相反,AC099850.3与M2巨噬细胞、单核细胞、NK 细胞和CD8+T细胞呈负相关,这可能是其致癌作用的原因。值得注意的是,在AC099850.3 以及关键免疫检查点分子(PD-1、PD-L1、PD-L2 和 CTLA4),使 AC099850.3 成为 HCC 潜在的免疫治疗靶点。
AC099850.3 可促进 HCC 细胞的恶性生物学行为,可能是 HCC 潜在的生物标志物和治疗靶点。
Background: LncRNA is a key factor influencing tumor development. The present study aimed to investigate the effect of a novel lncRNA on the progression of hepatocellular carcinoma (HCC). Methods: A candidate lncRNA in The Cancer Genome Atlas database was identified using limma and survival R packages. The effect of lncRNA AC099850. 3 on cell proliferation, apoptosis, migration, and invasion, as well as its association with immune cells in HCC were investigated.
Furthermore, the functional mechanisms of lncRNA AC099850. 3 in HCC were elucidated. Results: The aberrant expression of lncRNA AC099850. 3 was identified in tumor tissues and its prognostic relevance in HCC was determined. The results revealed that AC099850. 3 was highly expressed in HCC tissues and cell lines, and it predicted poor prognosis in patients with HCC.
Furthermore, knockdown of AC099850. 3 significantly suppressed the proliferation and metastatic potential of HCC cells, and promoted cell apoptosis in HCC cells. The results of gene set enrichment analysis revealed that the PI3K/AKT pathway was associated with the biological function of AC099850. 3, which was further validated by western blotting. PRR11 was identified as the target gene of AC099850. 3 and we established that AC099850. 3 acted as an oncogene in the PRR11/PI3K/AKT axis. Immune cell infiltration analyses results revealed that AC099850. 3 was positively correlated with T follicular helper cells, M0 macrophages, CD4 + memory T cells, and memory B cells.
Conversely, AC099850. 3 was negatively correlated with M2 macrophages, monocytes, natural killer cells, and CD8 + T cells, which could be responsible for its oncogenic effect. Of note, a significantly positive correlation was observed between AC099850. 3 and key immune checkpoint molecules (PD-1, PD-L1, PD-L2, and CTLA4) in the present study, making AC099850. 3 a potential immune therapeutic target for HCC. Conclusion: AC099850. 3 can promote malignant biological behavior of HCC cells, and could be a potential biomarker and therapeutic target for HCC.
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