Long non-coding RNAs (lncRNAs) have been shown to be vital players in a majority of physiological and pathological processes, including tumorigenesis and tumor progression. The aim of this study was to identify lncRNAs that can serve as biomarkers for cancer prognosis. Based on dosage sensitivity, we utilized the biological features of known cancer-related lncRNAs, and identified microRNA and transcription factor (miRNA-TF) co-regulatory motifs in an effort to establish a holistic analysis framework and predict new cancer prognosis-associated lncRNAs. We found that lncRNAs with low dosage sensitivity regulated by more than 3 types of co-regulatory motifs were more likely to be associated with cancer. By the use of the integrative analysis of 3035 tumor samples across 9 types of cancer, a total of 33 cancer prognosis-associated lncRNAs were identified. Additionally, on the basis of the miRNA-TF co-regulatory network, we also predicted potential small molecule drugs such as Glucocorticoid and Ginsenoside Rh2 for treating KIRC by targeting miRNA. This study explains the causes of abnormalities in the genome from a new perspective, and provides new clues for cancer diagnosis and prognosis, and research for anti-cancer drugs.

中文翻译：

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基于miRNA-TF共同调控基序和剂量敏感性，鉴定与癌症预后相关的lncRNA。

长的非编码RNA（lncRNA）已被证明在包括肿瘤发生和肿瘤进展在内的大多数生理和病理过程中起着至关重要的作用。这项研究的目的是鉴定可以用作癌症预后生物标志物的lncRNA。基于剂量敏感性，我们利用已知的癌症相关lncRNA的生物学特性，并鉴定了microRNA和转录因子（miRNA-TF）的共调控基序，以建立整体分析框架并预测与癌症预后相关的新的lncRNA。我们发现具有低剂量敏感性的lncRNAs受3种以上的共调控基序调控的可能性更大。通过对9种类型的癌症中的3035个肿瘤样本进行综合分析，总共鉴定出33种与癌症预后相关的lncRNA。此外，在miRNA-TF共同调控网络的基础上，我们还预测了潜在的小分子药物，例如糖皮质激素和人参皂苷Rh2可通过靶向miRNA来治疗KIRC。这项研究从一个新的角度解释了基因组异常的原因，并为癌症的诊断和预后以及抗癌药物的研究提供了新的线索。