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肺腺癌受 (和)双链调控的新型致癌靶点

: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of ( and ).

机构信息

Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.

MSD K.K., Tokyo 102-8667, Japan.

出版信息

Cells. 2020 Sep 11;9(9):2083. doi: 10.3390/cells9092083.

Abstract

Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of ( and ) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced or expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): = 0.1264 and 0.0316; overall survival (OS): = 0.0176 and 0.0756, respectively). Ectopic expression of these miRNAs attenuated LUAD cell proliferation, suggesting their tumor-suppressive roles. Our in silico analysis revealed 23 putative target genes of pre- in LUAD cells. Among these targets, high expressions of 19 genes were associated with worse prognoses in LUAD patients (OS: < 0.05). Notably, was regulated by both and in LUAD cells, and its aberrant expression was significantly associated with poor prognosis in LUAD patients (OS: = 0.0175; DFS: = 0.0276). knockdown using siRNAs suggested that elevated expression contributes to cancer progression. Aberrant FAM64A expression was detected in LUAD tissues by immunostaining. Taken together, our miRNA-based analysis might be effective for identifying prognostic and therapeutic molecules in LUAD.

摘要

肺腺癌(LUAD)是最具侵袭性的癌症,这些患者的预后不佳。我们发现,在几种癌症组织中,(和)的双链表达水平均显著受到抑制。对大型癌症基因组图谱(TCGA)数据集的分析表明,或表达降低与 LUAD 患者的预后不良相关(无病生存期(DFS):= 0.1264 和 0.0316;总生存期(OS):= 0.0176 和 0.0756)。这些 miRNA 的异位表达减弱了 LUAD 细胞的增殖,表明它们具有肿瘤抑制作用。我们的计算机分析揭示了 23 个在 LUAD 细胞中可能是前体的靶基因。在这些靶基因中,19 个基因的高表达与 LUAD 患者的预后不良相关(OS:< 0.05)。值得注意的是,在 LUAD 细胞中,同时受到和的调控,其异常表达与 LUAD 患者的不良预后显著相关(OS:= 0.0175;DFS:= 0.0276)。使用 siRNAs 进行 敲低表明,升高的表达有助于癌症进展。免疫染色检测到 LUAD 组织中存在异常的 FAM64A 表达。综上所述,我们基于 miRNA 的分析可能有助于识别 LUAD 中的预后和治疗分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabf/7564711/41dfb8608550/cells-09-02083-g001.jpg

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