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LncRNA AC099850.3 通过 PRR11/PI3K/AKT 轴促进肝细胞癌增殖和侵袭,并与患者预后相关

英文原题: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 AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11/PI3K/AKT axis and is associated with patients prognosis.

PubMed 2022/01/04(内容时间) J Cancer Q2 · IF 3.4(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Zhong F、Liu S、Hu D、Chen L
第一作者单位
Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha 410000, Hunan, China.China
通讯作者单位
Department of Anesthesiology, Hubei Cancer Hospital, Wuhan 430079, China.China
期刊
Journal of Cancer2022
原文标识
PubMed 35154469 · DOI 10.7150/jca.66092