利用内质网应激相关lncrna和LINC01011作为潜在治疗靶点建立肝癌特异性预后模型。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Xiao Du, Ning Wei, Anqi Wang, Guoping Sun
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引用次数: 0

摘要

肝癌是世界范围内的一种严重恶性肿瘤,长链非编码rna (lncRNAs)与肝癌的预后密切相关。目前尚不清楚与内质网应激(ERS)相关的lncrna如何影响肝癌预后。在这里,我们分析了来自癌症基因组图谱的RNA和临床数据,并从分子特征数据库中获取了ers相关基因。共表达分析确定了ers相关的lncrna, Cox回归分析以及最小绝对收缩和选择算子回归突出了三种用于预后模型的lncrna。根据中位风险评分,我们将患者分为两个风险组。高危组预后较差,这一发现在试验集中得到了验证。根据一致性聚类,将患者分为两个聚类,计算肿瘤微环境评分。突变负担高的患者预后更差。此外,免疫浸润分析表明高危人群中免疫细胞和检查点分子的突变更多。不同风险组的药物敏感性不同。选择LINC01011进行功能分析。集落形成实验和CCK-8实验表明,沉默LINC01011可抑制肝癌细胞的增殖。Transwell和scratch实验表明,沉默LINC01011抑制了肝癌细胞的迁移。Western blotting结果显示,抑制LINC01011可诱导细胞凋亡,同时抑制上皮-间质转化。这些发现证实了该预后模型的有效性,并表明LINC01011可以作为一个潜在的研究靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Liver cancer-specific prognostic model developed using endoplasmic reticulum stress-related LncRNAs and LINC01011 as a potential therapeutic target.

Liver cancer is a serious malignancy worldwide, and long noncoding RNAs (lncRNAs) have been implicated in its prognosis.It remains unclear how lncRNAs related to endoplasmic reticulum stress (ERS) influence liver cancer prognosis. Here, we analyzed RNA and clinical data from the Cancer Genome Atlas and sourced ERS-related genes from the Molecular Signatures Database. Co-expression analysis identified ERS-related lncRNAs, and Cox regression analysis as well as least absolute shrinkage and selection operator regression highlighted three lncRNAs for a prognostic model. Based on median risk scores, we classified patients into two risk groups. The high-risk group displayed poor prognosis, and this finding was validated in the test set. According to consistency clustering, the patients were assigned to two clusters, and tumor microenvironment scores were computed. Patients with a high mutation burden had worse outcomes. Furthermore, immune infiltration analysis indicated more immune cells and mutations in checkpoint molecules among high-risk individuals. Drug sensitivity varied between the risk groups. LINC01011 was selected for functional assays. Colony formation assay and CCK-8 assay revealed that silencing LINC01011 suppressed liver cancer cell proliferation. Transwell and scratch assays indicated that silencing LINC01011 inhibited liver cancer cell migration. Western blotting assay revealed that inhibiting LINC01011 induced apoptosis and simultaneously inhibited epithelial-mesenchymal transition. These findings confirm the validity of the prognostic model and indicate that LINC01011 could serve as a potential research target.

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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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