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:Identification of two downregulated circRNAs in patients with acute B-lymphocytic leukemia.
Identification of two downregulated circRNAs in patients with acute B-lymphocytic leukemia.
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急性B淋巴细胞白血病(B-ALL)死亡率高,目前尚无有效的治疗策略。鉴定B-ALL的诊断和预后生物标志物有助于开发新的治疗方法和药物,从而改善B-ALL患者的生存结局。
本研究旨在鉴定B-ALL患者中下调的环状RNA(circRNA)。通过RNA测序构建B-ALL细胞和正常人淋巴母细胞的circRNA表达谱。使用Database for Annotation, Visualization and Integrated Discovery进行基因本体富集分析和京都基因与基因组百科全书通路分析。
此外,采用逆转录定量(RT-q)PCR检测下调circRNA的表达水平。共鉴定出263个差异表达的circRNA,其中76个上调,187个下调。上调的circRNA主要富集于“大分子修饰”、“蛋白质修饰”和“细胞蛋白质修饰过程”,而下调的circRNA主要富集于“RNA生物合成过程的负调控”、“NK 细胞介导的细胞毒性”和“病毒致癌”。RT-qPCR分析显示,微阵列分析中鉴定的两个下调circRNA(hsa_circ_0000745和chr15:87949594-87966067-)在Ball-1细胞和B-ALL骨髓样本中也显著下调。因此,这些circRNA可作为B-ALL患者的生物标志物。
Acute B-lymphocytic leukemia (B-ALL) is associated with a high mortality rate, with no effective treatment strategies available. The identification of diagnostic and prognostic biomarkers of B-ALL can contribute to the development of novel therapeutic methods and drugs, which can improve the survival outcomes of patients with B-ALL.
The present study aimed to identify downregulated circular RNAs (circRNAs) in patients with B-ALL. RNA sequencing was performed to construct the circRNA expression profiles in B-ALL cells and normal human lymphoblasts. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses.
In addition, reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of the downregulated circRNAs. A total of 263 differentially expressed circRNAs were identified, including 76 upregulated and 187 downregulated circRNAs, respectively.
The upregulated circRNAs were mainly enriched in 'macromolecule modification', 'protein modification' and 'cellular protein modification processes', while the downregulated circRNAs were mainly enriched in the 'negative regulation of RNA biosynthetic processes', 'natural killer cell-mediated cytotoxicity' and 'viral carcinogenesis'.
RT-qPCR analysis demonstrated that two of the downregulated circRNAs (hsa_circ_0000745 and chr15:87949594-87966067-), identified during microarray analysis were also significantly downregulated in Ball-1 cells and B-ALL bone marrow samples.
Thus, these circRNAs may serve as biomarkers for patients with B-ALL.
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