Identification and Characterization of TF-lncRNA Regulatory Networks Involved in the Tumorigenesis and Development of Adamantinomatous Craniopharyngioma

Abstract

Craniopharyngiomas (CPs) are rare tumors arising from the sellar region. Although the best outcome for patients with one subtype, adamantinomatous craniopharyngioma (ACP), is obtained by gross total resection, little is known about the roles of long noncoding RNAs (lncRNAs) and transcription factors (TFs) in ACP tumorigenesis. In total, 12 human ACP and 5 control samples were subjected to transcriptome-level sequencing. We built an integrated algorithm for identifying lncRNAs and TFs regulating the CP-related pathway. Furthermore, ChIP-Seq datasets with binding domain information were used to further verify and identify TF-lncRNA correlations. RT–PCR and immunohistochemistry staining were performed to validate the potential targets. Five pathways associated with ACP were identified and defined by an extensive literature search. Based on the specific pathways and the whole gene expression profile, 266 ACP-related lncRNAs and 39 TFs were identified by our integrating algorithm. Comprehensive analysis of the ChIP-Seq datasets revealed that 29 TFs were targeted by 12000 lncRNAs in a wide range of tissues, including 161 ACP-related lncRNAs that were identified by the computational method. These 29 TFs and 161 lncRNAs, constituting 1004 TF-lncRNA pairs, were shown to potentially regulate different ACP-related pathways. A total of 232 TF-lncRNA networks were consequently established based on differential gene expression. Validation by RT–PCR and immunohistochemistry staining revealed positive expression of the ACP-related TFs E2F2 and KLF5 in ACP. Moreover, the expression of the lncRNA RP11-360P21.2 was shown to be upregulated in ACP tissues. In this study, we introduced an integrated algorithm for identifying lncRNAs and TFs regulating the ACP-related pathway. This is the first comprehensive study to systematically investigate the potential TF and lncRNA regulatory network in ACP. The resulting data serve as a valuable resource for understanding the mechanisms underlying ACP-related lncRNAs and TFs.

LncRNA RP11-10E18.7 cooperates with lncRNA RP11-481C4.2 to affect the overall survival of breast cancer patients: a TCGA-based retrospective study

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Long Non-Coding RNA AL139385.1 as a Novel Prognostic Biomarker in Lung Adenocarcinoma

“…Increasing evidence revealed that lncRNAs are aberrantly regulated in various cancer types and may act crucial roles in tumor progression of cell migration, proliferation, genomic stability, and survival in LUAD ( 5 – 7 ). Owing to lncRNAs are involved in the lung adenocarcinoma (LUAD)-related gene expression and also be regulated by transcription factors in diverse human cancer progression ( 8 ). It have been confirmed that lncRNAs to compete with microRNAs (miRNAs) as a molecular sponge result in the degradation of target mRNAs ( 9 ).…”

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

“…Meanwhile, the IL-6 inhibitor, tocilizumab, was also proven to be effective in some specific cases ( 7 ). In addition, our previous studies also investigated essential transcript factor (TF)–lncRNA pairs based on an integrated algorithm, which provided new insights into the underlying mechanism of ACP development ( 8 ). Currently, the accumulation of beta-catenin caused by CTNNB1 mutations has been recognized as the driver mutations in ACPs ( 9 – 11 ).…”