A pan‐cancer atlas of cancer hallmark‐associated candidate driver lnc<scp>RNA</scp>s

Deng, Yulan; Luo, Shangyi; Zhang, Xinxin; Zou, Chaoxia; Yuan, Huating; Liao, Gaoming; Xu, Liwen; Deng, Chunyu; Lan, Yujia; Zhao, Tingting; Gao, Xu; Xiao, Yun; Li, Xia

doi:10.1002/1878-0261.12381

Cited by 18 publications

(16 citation statements)

References 110 publications

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“…In a previous study, Bing et al, (2017) identified several lncRNAs altered at genomics level in lung cancer. LINC00885 gene amplification was among the highly altered lncRNAs in 38% of lung squamous cell carcinomas [ 18 ]. More recently, Deng et al (2018) identified 378 candidate driver lncRNAs through integrative analysis of CNA data obtained from TCGA Pan-Cancer dataset [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

Abba

Canzoneri

Gurruchaga

et al. 2020

IJMS

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Long intergenic non-protein coding RNA 885 (LINC00885) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by LINC00885 in non-invasive and invasive breast cancer models. We determined that LINC00885 induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by LINC00885, which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. LINC00885 silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as EREG, CMYC, CCND1 and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high LINC00885 expression and worse overall survival in patients with primary invasive breast carcinomas (p = 0.024), suggesting that the pro-tumorigenic effects of LINC00885 overexpression persist post-invasion. We conclude that LINC00885 behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.

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Section: Resultsmentioning

confidence: 99%

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

Abba

Canzoneri

Gurruchaga

et al. 2020

IJMS

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“… 2 The prevalent focal and arm-level SCNAs affected large cancer genome regions that not only included protein-coding genes (PGs) but also non-coding regions. 3 , 4 How to elucidate the functional roles of SCNAs in cancers and how these SCNAs disorder cellular homeostasis and further promote cancer progression are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers

Ping

Zhou

et al. 2020

Molecular Therapy - Nucleic Acids

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Somatic copy-number alterations (SCNAs) drive tumor growth and evolution. However, the functional roles of SCNAs across the genome are still poorly understood. We provide an integrative strategy to characterize the functional roles of driver SCNAs in cancers based on dysregulated competing endogenous RNA (ceRNA) networks. We identified 44 driver SCNAs in lower-grade glioma (LGG). The dysregulated patterns losing all correlation relationships dominated dysregulated ceRNA networks. Homozygous deletion of six genes in 9p21.3 characterized an LGG subtype with poor prognosis and contributed to the dysfunction of cancer-associated pathways in a complementary way. The pan-cancer analysis showed that different cancer types harbored different driver SCNAs through dysregulating the crosstalk with common ceRNAs. The same SCNAs destroyed their ceRNA networks through different miRNA-mediated ceRNA regulations in different cancers. Additionally, some SCNAs performed different functional mechanisms in different cancers, which added another layer of complexity to cancer heterogeneity. Compared with previous methods, our strategy could directly dissect functional roles of SCNAs from the view of ceRNA networks, which not only complemented the functions of protein-coding genes but also provided a new avenue to characterize the functions of noncoding RNAs. Also, our strategy could be applied to more types of cancers to identify pathogenic mechanism driven by the SCNAs.

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“…Among DEGs, we focused on genes involved in reprogramming energy metabolism as well as genes related to malignant tissue development. The reprogramming energy metabolism-related genes were identified by hallmark-associated GO terms in our previous research ( Deng et al, 2018 ). Then, we performed the univariable Cox regression analysis to select genes associated with overall survival in the training cohort.…”

Section: Methodsmentioning

confidence: 99%

Transcriptome analysis reveals a reprogramming energy metabolism-related signature to improve prognosis in colon cancer

Zhang

Lan

et al. 2020

PeerJ

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Although much progress has been made to improve treatment, colon cancer remains a leading cause of cancer death worldwide. Metabolic reprogramming is a significant ability of cancer cells to ensure the necessary energy supply in uncontrolled proliferation. Since reprogramming energy metabolism has emerged as a new hallmark of cancer cells, accumulating evidences have suggested that metabolism-related genes may serve as key regulators of tumorigenesis and potential biomarkers. In this study, we analyzed a set of reprogramming energy metabolism-related genes by transcriptome analysis in colon cancer and revealed a five-gene signature that could significantly predict the overall survival. The reprogramming energy metabolism-related signature could distinguish patients into high-risk and low-risk groups with significantly different survival times (P = 0.0011; HR = 1.92; 95% CI [1.29–2.87]). Its prognostic value was confirmed in another two independent colon cancer cohorts (P = 5.2e–04; HR = 2.09, 95%; CI [1.37–3.2] for GSE17538 and P = 3.8e−04; HR = 2.08, 95% CI [1.37–3.16] for GSE41258). By multivariable analysis, we found that the signature was independent of clinicopathological features. Its power in promoting risk stratification of the current clinical stage was then evaluated by stratified analysis. Moreover, the signature could improve the power of the TNM stage for the prediction of overall survival and could be used in patients who received adjuvant chemotherapy. Overall, our results demonstrated the important role of the reprogramming energy metabolism-related signature in promoting stratification of high-risk patients, which could be diagnostic of adjuvant therapy benefit.

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A pan‐cancer atlas of cancer hallmark‐associated candidate driver lncRNAs

Cited by 18 publications

References 110 publications

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

Dissecting the Functional Mechanisms of Somatic Copy-Number Alterations Based on Dysregulated ceRNA Networks across Cancers

Transcriptome analysis reveals a reprogramming energy metabolism-related signature to improve prognosis in colon cancer

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