College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Mol Omics. 2019 Oct 7;15(5):361-373. doi: 10.1039/c9mo00089e.
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.
长链非编码 RNA（lncRNAs）已被证明在大多数生理和病理过程中发挥着至关重要的作用，包括肿瘤发生和肿瘤进展。本研究旨在鉴定可作为癌症预后生物标志物的 lncRNAs。基于剂量敏感性，我们利用已知与癌症相关的 lncRNAs 的生物学特征，确定了 microRNA 和转录因子（miRNA-TF）共同调控基序，以建立一个整体分析框架并预测新的癌症预后相关 lncRNAs。我们发现，受 3 种以上共调控基序调控的低剂量敏感性 lncRNAs 更有可能与癌症相关。通过对 9 种癌症的 3035 个肿瘤样本的综合分析，共鉴定出 33 个与癌症预后相关的 lncRNAs。此外，基于 miRNA-TF 共调控网络，我们还通过靶向 miRNA 预测了潜在的小分子药物，如糖皮质激素和人参皂苷 Rh2，用于治疗 KIRC。这项研究从新的角度解释了基因组异常的原因，为癌症诊断和预后以及抗癌药物的研究提供了新的线索。
