Sarcomas are a broad family of cancers that arise from cells of mesenchymal origin in virtually every tissue of the body. Some transcription factors (TFs) have been reported to be involved in the pathogenesis and metastasis of sarcomas. The expression of certain long noncoding RNAs (lncRNAs) has been correlated with the degree of cancer prognosis. There is an urgent need to effectively integrate TFs and lncRNA/microRNA/mRNA regulatory axis and further identify more key regulators that play crucial roles in sarcomas. We performed a network-based computational analysis to investigate the lncRNA-TF cross talks via integrating lncRNA-TF ceRNA interactions and TF-TF protein–protein interactions. Multiple topology analyses were performed to the sarcomas-related global lncRNA-TF network. Several lncRNAs or TFs with central topology structures were identified as key regulators and used to locate a hub-associated lncRNA-TF subnetwork. Three functional modules were identified from the sarcomas-related global lncRNA-TF network, which have shown significant pathway enrichment and prognosis capability. The lncRNAs and TFs of these modules were shown to participate in sarcoma-related biological phenomena through involving in mitogen-activated protein kinases (MAPK), Jak-STAT, and transforming growth factor (TGF-beta) signaling pathways. More importantly, a subset of core lncRNA-TF cross talks that might form positive feedback loops to control biological processes of sarcomas was identified. These core lncRNA-TF positive feedback loops showed more TF binding affinity than other lncRNAs. All the results can help us uncover the molecular mechanism of sarcomas and provide a novel way for diagnosis biomarker and therapeutic target identification.

中文翻译：

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肉瘤中新型lncRNA-TF调控串扰的全面分析和核心lncRNA-TF反馈环的鉴定。

肉瘤是广泛的癌症家族，其起源于几乎所有人体组织中的间充质来源的细胞。据报道，一些转录因子（TFs）参与肉瘤的发病和转移。某些长非编码RNA（lncRNA）的表达已与癌症的预后程度相关。迫切需要有效整合TF和lncRNA / microRNA / mRNA调控轴，并进一步确定在肉瘤中起关键作用的更多关键调控因子。我们进行了基于网络的计算分析，以通过整合lncRNA-TF ceRNA相互作用和TF-TF蛋白质-蛋白质相互作用来研究lncRNA-TF串扰。对与肉瘤相关的全球lncRNA-TF网络进行了多种拓扑分析。具有中央拓扑结构的几个lncRNA或TF被确定为关键调控因子，并用于定位与集线器相关的lncRNA-TF子网。从肉瘤相关的全球lncRNA-TF网络中鉴定出三个功能模块，它们显示出显着的途径富集和预后能力。这些模块的lncRNA和TF通过参与有丝分裂原激活的蛋白激酶而参与肉瘤相关的生物学现象（MAPK），Jak-STAT和转化生长因子（TGF-beta）信号通路。更重要的是，确定了可能形成阳性反馈环以控制肉瘤生物学过程的核心lncRNA-TF串扰的子集。这些核心lncRNA-TF正反馈环显示出比其他lncRNA更多的TF结合亲和力。所有结果可帮助我们揭示肉瘤的分子机制，并为诊断生物标志物和确定治疗靶标提供一种新途径。