Long noncoding RNAs in cancer: From discovery to therapeutic targets

Choudhari, Ramesh; Sedano, Melina J.; Harrison, A.; Subramani, Ramadevi; Lin, Ken Y.; Ramos, Enrique; Lakshmanaswamy, Rajkumar; Gadad, Shrikanth S.

doi:10.1016/bs.acc.2019.08.003

Cited by 107 publications

(87 citation statements)

References 277 publications

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“…Dysregulation of lncRNAs has been found to be relevant for neurological, cardiovascular, and developmental disorders, as well as cancer [ 15 ]. In fact, growing evidence shows that lncRNAs drive important cancer phenotypes through their interactions with other cellular macromolecules, such as RNA, DNA, and protein [ 16 ]. To date, A-to-I RNA editing in lncRNAs has been poorly investigated and, despite recent studies reporting that RNA editing may impact the secondary structure of RNA and the lncRNA–miRNA interactions, the role of the edited lncRNAs remains largely unknown [ 9 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

De Novo A-to-I RNA Editing Discovery in lncRNA

Silvestris

Scopa

Hanchi

et al. 2020

Cancers

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Background: Adenosine to inosine (A-to-I) RNA editing is the most frequent editing event in humans. It converts adenosine to inosine in double-stranded RNA regions (in coding and non-coding RNAs) through the action of the adenosine deaminase acting on RNA (ADAR) enzymes. Long non-coding RNAs, particularly abundant in the brain, account for a large fraction of the human transcriptome, and their important regulatory role is becoming progressively evident in both normal and transformed cells. Results: Herein, we present a bioinformatic analysis to generate a comprehensive inosinome picture in long non-coding RNAs (lncRNAs), using an ad hoc index and searching for de novo editing events in the normal brain cortex as well as in glioblastoma, a highly aggressive human brain cancer. We discovered >10,000 new sites and 335 novel lncRNAs that undergo editing, never reported before. We found a generalized downregulation of editing at multiple lncRNA sites in glioblastoma samples when compared to the normal brain cortex. Conclusion: Overall, our study discloses a novel layer of complexity that controls lncRNAs in the brain and brain cancer.

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Section: Introductionmentioning

confidence: 99%

De Novo A-to-I RNA Editing Discovery in lncRNA

Silvestris

Scopa

Hanchi

et al. 2020

Cancers

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“…Accumulating evidence has shown that lncRNAs act as important regulators related to tumorigenesis and cancer progression. [25][26][27] However, the function of lncRNAs, including MIR194-2HG, in HCC cells has not been totally elucidated. MIR194-2HG was first reported to be upregulated in bladder cancer, 17 and its dysregulation might be related to cancer progression.…”

Section: Discussionmentioning

confidence: 99%

<p>LncRNA MIR194-2HG Promotes Cell Proliferation and Metastasis via Regulation of miR-1207-5p/TCF19/Wnt/β-Catenin Signaling in Liver Cancer</p>

Xu¹,

Zhu²,

Liu³

et al. 2020

OTT

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LncRNAs play an important role in tumorigenesis and cancer progression in liver cancer. Although many lncRNAs have been reported, the role of MIR194-2HG and the underlying mechanism mediated by it are still largely unknown in HCC. This study aimed to investigate the biological role and mechanism of MIR194-2HG in liver cancer. Materials and Methods: The expression of MIR194-2HG was determined in liver cancer tissues and cells by RT-qPCR. The overall survival rate of MIR194-2HG was analyzed by Kaplan-Meier survival analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays were carried out to detect cell migration and invasion. Western blotting was used to quantify the levels of all proteins. The regulatory mechanism of the MIR194-2HG/miR-1207-5p/TCF19 axis in liver cancer was investigated by dual-luciferase activity reporter assay, Kaplan-Meier survival analysis, and Western blotting. Results: MIR194-2HG was upregulated in liver cancer tissues and cell lines. Liver cancer patients with higher expression of MIR194-2HG revealed poor overall survival compared with those who had lower expression of MIR194-2HG. MIR194-2HG promoted the proliferation, migration, and invasion of HepG2 and Huh7 cells by acting as a ceRNA mechanism for the miR-1207-5p/TCF19 axis to activate the Wnt/β-catenin signaling pathway. Conclusion: MIR194-2HG acts in an oncogenic role and activates the Wnt/β-catenin signaling pathway via a miR-1207-5p/TCF19 axis-mediated mechanism, which provides a novel avenue for diagnostic or therapeutic interventions in liver cancer.

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“…They can regulate gene expression through epigenetic regulation, transcriptional regulation and posttranscriptional regulation and are involved in biological processes such as the regulation of tumor cell cycle, cell proliferation, differentiation, apoptosis and migration [9][10][11]. An increasing number of lncRNAs have been shown to be abnormally expressed in cancers and have a signi cant correlation with treatment and clinical prognosis, providing the possibility for lncRNAs to become novel tumor biomarkers and therapeutic targets [12]. For example, the level of lncRNA small nucleolar RNA host gene 14 (SNHG14) is signi cantly increased in ovarian cancer tissues, and the inhibition of SNHG14 signi cantly inhibits the migration and invasion of cells [13].…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine-related lncRNAs as a biomarker for predicting the prognosis and immune microenvironment of clear cell renal cell carcinoma

Qiu

Wang

Fan

et al. 2021

Preprint

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Background: Patients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. This study uses bioinformatics analysis to identify N6-methyladenosine-related lncRNAs (m6A-related lncRNAs) as new prognostic biomarkers for ccRCC.Methods: Gene expression data and related clinical information of ccRCC patients were extracted from the Cancer Genome Atlas Database. m6A-related lncRNAs were obtained by co-expression analysis. Univariate Cox regression analysis was performed on these lncRNAs to find the prognostic-related m6A-related lncRNAs, and consensus clustering analysis was performed. The prognostic signature was screened by LASSO regression and a prognostic model was constructed. The predictive performance of the prognostic model was evaluated and validated by survival analysis and ROC curve analysis, etc. In addition, we also systematically analyzed the expression of immune checkpoints and immune cell infiltration in ccRCC patients.Results: First, 27 m6A-related lncRNAs associated with prognosis were identified, which were significantly differentially expressed between tumor and normal tissues. Consensus clustering analysis indicated that cluster 2 was associated with poor prognosis, low stromal score, high expression of PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT, and immunosuppressive cell infiltration. The signaling pathways related to tumor progression, drug resistance, and angiogenesis and biological processes related to protein methylation and phosphatidic acid metabolism are significantly enriched in cluster 2. Subsequently, LASSO regression analysis was used to construct a prognostic risk model based on 7 m6A-related lncRNAs signature, which can be used as an independent prognostic indicator. After a series of analyses, it was shown that this model had good sensitivity and specificity, can predict the prognosis of patients with different clinical stratifications and was associated with the progression of ccRCC. The expression levels of immune checkpoints were significantly increased in high-risk patients, and there was a certain correlation between the risk score and immune cell infiltration. Conclusions: In summary, we constructed and validated a risk model that can independently predict the prognosis of ccRCC patients and reflect the immune microenvironment based on m6A-related lncRNAs; the model is conducive to the screening of biomarkers of ccRCC prognosis and may have the potential to reflect the response of ccRCCs to immunotherapy.

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Long noncoding RNAs in cancer: From discovery to therapeutic targets

Cited by 107 publications

References 277 publications

De Novo A-to-I RNA Editing Discovery in lncRNA

De Novo A-to-I RNA Editing Discovery in lncRNA

<p>LncRNA MIR194-2HG Promotes Cell Proliferation and Metastasis via Regulation of miR-1207-5p/TCF19/Wnt/β-Catenin Signaling in Liver Cancer</p>

N6-methyladenosine-related lncRNAs as a biomarker for predicting the prognosis and immune microenvironment of clear cell renal cell carcinoma

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