Identification and comprehensive characterization of lncRNAs with copy number variations and their driving transcriptional perturbed subpathways reveal functional significance for cancer

Abstract

Numerous studies have shown that copy number variation (CNV) in lncRNA regions play critical roles in the initiation and progression of cancer. However, our knowledge about their functionalities is still limited. Here, we firstly provided a computational method to identify lncRNAs with copy number variation (lncRNAs-CNV) and their driving transcriptional perturbed subpathways by integrating multidimensional omics data of cancer. The high reliability and accuracy of our method have been demonstrated. Then, the method was applied to 14 cancer types, and a comprehensive characterization and analysis was performed. LncRNAs-CNV had high specificity in cancers, and those with high CNV level may perturb broad biological functions. Some core subpathways and cancer hallmarks widely perturbed by lncRNAs-CNV were revealed. Moreover, subpathways highlighted the functional diversity of lncRNAs-CNV in various cancers. Survival analysis indicated that functional lncRNAs-CNV could be candidate prognostic biomarkers for clinical applications, such as ST7-AS1, CDKN2B-AS1 and EGFR-AS1. In addition, cascade responses and a functional crosstalk model among lncRNAs-CNV, impacted genes, driving subpathways and cancer hallmarks were proposed for understanding the driving mechanism of lncRNAs-CNV. Finally, we developed a user-friendly web interface-LncCASE (http://bio-bigdata.hrbmu.edu.cn/LncCASE/) for exploring lncRNAs-CNV and their driving subpathways in various cancer types. Our study identified and systematically characterized lncRNAs-CNV and their driving subpathways and presented valuable resources for investigating the functionalities of non-coding variations and the mechanisms of tumorigenesis.

Characterizing the Copy Number Variation of Non-Coding RNAs Reveals Potential Therapeutic Targets and Prognostic Markers of LUSC

“…Therefore, tumor patients were divided into a group with CNV in the lncRNA and a control group based on lncRNA copy number profiles. Moreover, lncRNAs tended to undergo overall copy number amplification in LUSC ( Figure 1B ), which is contrary to a previous study suggesting that copy number deletion pattern of the lncRNAs was widely observed in various cancer types ( Xu et al, 2020 ). Furthermore, we identified 372 lncRNAs whose expression levels (FPKM) are driven by CNV ( Figure 1C ).…”

“…Genetic variation in the lncRNA region, such as single-nucleotide variation, somatic mutation, and copy number variation (CNV), may affect the expression level of the gene and its target genes, which may contribute to tumor occurrence and development ( Wang et al, 2020 ). For example, lncRNAs with CNVs drive transcriptional perturbed functional pathways ( Xu et al, 2020 ), and single-nucleotide variation in lncRNA regulates cancer-related pathways through ceRNA mechanism ( Zhang et al, 2021 ).…”

Population-level annotation of lncRNA transcription in Arabidopsis reveals extensive variation associated with transposable element-like silencing

“…LncRNAs are known to sometimes originate from transposable elements (TEs) (Zhu et al, 2022; Kapusta et al, 2013), yet what implications this has for their expression, epigenetics and variation is not well known. Similarly, while aberrant lncRNA copy number has been connected to disease and other phenotypes (Xu et al, 2020; Athie et al, 2020), general information about lncRNA copy number and its consequences is missing, in particular in plants.…”

LncRNA ST7-AS1 is a Potential Novel Biomarker and Correlated With Immune Infiltrates for Breast Cancer

“…LncRNA ST7-AS1 is a newly discovered one located on 7q31.2 (Qin et al, 2019). LncRNA ST7-AS1 with Copy Number Variations (CNVs) can cause gene disorder in downstream cancers, which is also strongly linked to proliferation, apoptosis, and cell migration belonging to the biological processes of cancer (Xu et al, 2019). Based on current evidence, ST7-AS1 has a strong correlation with human glioma and laryngeal squamous cell carcinoma (Liu et al, 2015;Tian et al, 2017).…”