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Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival.

泛癌症分析揭示了调控肿瘤发生和患者生存的两股 microRNA 的协同性。

  • 影响因子:12.19
  • DOI:10.1038/s41467-020-14713-2
  • 作者列表:"Mitra R","Adams CM","Jiang W","Greenawalt E","Eischen CM
  • 发表时间:2020-02-20
Abstract

:Recently, both 5p and 3p miRNA strands are being recognized as functional instead of only one, leaving many miRNA strands uninvestigated. To determine whether both miRNA strands, which have different mRNA-targeting sequences, cooperate to regulate pathways/functions across cancer types, we evaluate genomic, epigenetic, and molecular profiles of >5200 patient samples from 14 different cancers, and RNA interference and CRISPR screens in 290 cancer cell lines. We identify concordantly dysregulated miRNA 5p/3p pairs that coordinately modulate oncogenic pathways and/or cell survival/growth across cancers. Down-regulation of both strands of miR-30a and miR-145 recurrently increased cell cycle pathway genes and significantly reduced patient survival in multiple cancers. Forced expression of all four strands show cooperativity, reducing cell cycle pathways and inhibiting lung cancer cell proliferation and migration. Therefore, we identify miRNA whose 5p/3p strands function together to regulate core tumorigenic processes/pathways and reveal a previously unknown pan-cancer miRNA signature with patient prognostic power.

摘要

: 最近,5p 和 3p miRNA 链都被认为是功能性的,而不是只有一条,使得许多 miRNA 链未被研究。为了确定具有不同 mRNA 靶向序列的两个 miRNA 链是否合作调节跨癌症类型的通路/功能,我们评估了基因组学、表观遗传学、和来自 14 种不同癌症的> 5200 个患者样本的分子图谱,以及 290 个癌细胞系的 RNA 干扰和 CRISPR 筛选。我们确定了协调调节致癌通路和/或跨癌症细胞存活/生长的一致失调的 miRNA 5p/3p 对。MiR-30a 和 miR-145 两条链的下调反复增加细胞周期通路基因,显著降低多种癌症患者的生存率。所有四条链的强制表达表现出协同性,减少细胞周期通路,抑制肺癌细胞增殖和迁移。因此,我们确定了 5p/3p 链共同发挥功能调节核心致瘤过程/通路的 miRNA,并揭示了一个以前未知的具有患者预后能力的泛癌 miRNA 标记。

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影响因子:6.93
发表时间:2020-04-01
DOI:10.1002/ijc.32847
作者列表:["Abrahamsson H","Jensen BV","Berven LL","Nielsen DL","Šaltytė Benth J","Johansen JS","Larsen FO","Johansen JS","Ree AH"]

METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.

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影响因子:4.88
发表时间:2020-03-01
DOI:10.1016/j.ecoenv.2019.110098
作者列表:["Suvina V","Kokulnathan T","Wang TJ","Balakrishna RG"]

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影响因子:6.50
发表时间:2020-03-31
来源期刊:Cancer letters
DOI:10.1016/j.canlet.2019.12.039
作者列表:["Zhou Z","Zhou Q","Wu X","Xu S","Hu X","Tao X","Li B","Peng J","Li D","Shen L","Cao Y","Yang L"]

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