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长链非编码RNA AC099850.3通过PRR11/PI3K/AKT轴促进肝细胞癌的增殖和侵袭,并与患者预后相关。

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

作者信息

Zhong Fangjing, Liu Sheng, Hu Donghai, Chen Liwen

机构信息

Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha 410000, Hunan, China.

Department of Hepatobiliary Surgery, Hubei Cancer Hospital, Wuhan 430079, China.

出版信息

J Cancer. 2022 Jan 4;13(3):1048-1060. doi: 10.7150/jca.66092. eCollection 2022.

Abstract

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). 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. 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. 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. AC099850.3 can promote malignant biological behavior of HCC cells, and could be a potential biomarker and therapeutic target for HCC.

摘要

长链非编码RNA(lncRNA)是影响肿瘤发展的关键因素。本研究旨在探究一种新型lncRNA对肝细胞癌(HCC)进展的影响。使用limma和生存R包在癌症基因组图谱数据库中鉴定出一个候选lncRNA。研究了lncRNA AC099850.3对细胞增殖、凋亡、迁移和侵袭的影响,以及它与HCC中免疫细胞的关联。此外,阐明了lncRNA AC099850.3在HCC中的功能机制。鉴定了lncRNA AC099850.3在肿瘤组织中的异常表达,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,且预测HCC患者预后不良。此外,敲低AC099850.3可显著抑制HCC细胞的增殖和转移潜能,并促进HCC细胞凋亡。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,蛋白质免疫印迹进一步验证了这一点。PRR11被鉴定为AC099850.3的靶基因,且我们证实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与滤泡辅助性T细胞、M0巨噬细胞、CD4记忆性T细胞和记忆性B细胞呈正相关。相反,AC099850.3与M2巨噬细胞、单核细胞、自然杀伤细胞和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,本研究中观察到AC099850.3与关键免疫检查点分子(PD-1、PD-L1、PD-L2和CTLA4)之间存在显著正相关,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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74c0/8824888/eace0fe976e2/jcav13p1048g001.jpg

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