METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Feb. 28, 2020

Abstract Background N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulation in eukaryotic cells. However, understanding of m6A colorectal cancer (CRC) very limited. We designed this study to investigate role CRC. Methods Expression level METTL14 was extracted from public database and tissue array clinical relevance Next, gain/loss function experiment used define progression Moreover, transcriptomic sequencing (RNA-seq) applied screen potential targets METTL14. The specific binding between presumed target verified by pull-down immunoprecipitation (RIP) assay. Furthermore, rescue methylated (Me-RIP) were performed uncover mechanism. Results Clinically, loss correlated with unfavorable prognosis CRC patients. Functionally, knockdown drastically enhanced proliferative invasive ability cells vitro promoted tumorigenicity metastasis vivo. Mechanically, RNA-seq Me-RIP identified lncRNA XIST as downstream Knockdown substantially abolished augmented expression. we found that m6A-methylated recognized YTHDF2, a reader protein, mediate degradation . Consistently, expression negatively YTHDF2 tissues. Conclusion Our findings highlight prognostic value extend importance epigenetics biology.

Language: Английский

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Long Non-Coding RNAs: The Regulatory Mechanisms, Research Strategies, and Future Directions in Cancers

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: Dec. 18, 2020

The development and application of whole genome sequencing technology has greatly broadened our horizons on the capabilities long non-coding RNAs (lncRNAs). LncRNAs are more than 200 nucleotides in length lack protein-coding potential. Increasing evidence indicates that lncRNAs exert an irreplaceable role tumor initiation, progression, as well metastasis, novel molecular biomarkers for diagnosis prognosis cancer patients. Furthermore, pathways they influence might represent promising therapeutic targets a number tumors. Here, we discuss recent advances understanding specific regulatory mechanisms lncRNAs. We focused signal, decoy, guide, scaffold functions at epigenetic, transcription, post-transcription levels cells. Additionally, summarize research strategies used to investigate roles tumors, including screening, characteristic analyses, functional studies, This review will provide short but comprehensive description lncRNA thus accelerating clinical implementation targets.

Language: Английский

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Biological Function of Long Non-coding RNA (LncRNA) Xist

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 10, 2021

Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator cell growth development. Despites its original roles X-chromosome dosage compensation, Xist also participates the development tumor other human diseases by functioning competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress understanding cellular functions mammalian cells discussed current knowledge regarding ceRNA network various diseases. are transcripts more than 200 nt length without apparent protein-coding capacity (Furlan Rougeulle, 2016; Maduro et al., 2016). These believed to be transcribed approximately 98-99% regions genome (Derrien 2012; Fu, 2014; Montalbano 2017; Slack Chinnaiyan, 2019), well large genomic regions, such exonic, tronic, intergenic regions. Hence, lncRNAs divided into eight categories: Intergenic lncRNAs, Intronic Enhancer Promoter Natural antisense/sense Small nucleolar RNA-ended (sno-lncRNAs), Bidirectional non-poly(A) (Ma 2013; Devaux 2015; St Laurent Chen, Quinn Chang, Richard Eichhorn, 2018; Connerty 2020). A range has suggested function key regulators crucial functions, including proliferation, differentiation, apoptosis, migration, invasion, regulating level target genes via epigenomic, or post-transcriptional approaches (Cao 2018). Moreover, detected body fluids were serve potential biomarkers for diagnosis, prognosis, monitoring disease progression, act novel drug targets therapeutic exploitation (Jiang W. Zhou 2019a). set 15,000-20,000 sequences localized X chromosome inactivation center (XIC) Xq13.2 (Brown 1992; Debrand 1998; Kay, Lee da Rocha Heard, Yang Z. Brockdorff, 2019). Previous studies have indicated (XCI), resulting inheritable silencing one X-chromosomes during female Also, it vital regulatory whole spectrum (notably cancer) can used diagnostic prognostic biomarker clinic (Liu 2018b; Deng 2019; Dinescu Mutzel Schulz, 2020; Patrat Wang 2020a). particular, been demonstrated involved multiple types tumors brain tumor, Leukemia, lung cancer, breast liver with prominent examples outlined Table 1. It was (Chaligne 2018) contributed diseases, pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, osteoarthritis chondrocytes, details found 2. This review summarizes on mechanisms both compensation pathogenesis (especially processes, focus disease.

Language: Английский

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Correction to: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway

Genome Medicine, Journal Year: 2021, Volume and Issue: 13(1)

Published: Feb. 11, 2021

An amendment to this paper has been published and can be accessed via the original article.

Language: Английский

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Long non-coding RNA and RNA-binding protein interactions in cancer: Experimental and machine learning approaches

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 325 - 345

Published: May 25, 2022

Understanding the complex and specific roles played by non-coding RNAs (ncRNAs), which comprise bulk of genome, is important for understanding virtually every hallmark cancer. This large group molecules plays pivotal in key regulatory mechanisms various cellular processes. Regulatory mechanisms, mediated long RNA (lncRNA) RNA-binding protein (RBP) interactions, are well documented several types Their effects enabled through networks affecting lncRNA RBP stability, metabolism including N6-methyladenosine (m6A) alternative splicing, subcellular localization, numerous other involved In this review, we discuss reciprocal interplay between lncRNAs RBPs their involvement epigenetic regulation via histone modifications, as role resistance to cancer therapy. Other aspects structural domains, provide a deeper knowledge on how interact exert biological functions. addition, current state-of-the-art knowledge, facilitated machine deep learning approaches, unravels such interactions better details further enhance our field, potential harness RNA-based therapeutics an treatment modality discussed.

Language: Английский

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Long non-coding RNAs in lung cancer: Unraveling the molecular modulators of MAPK signaling

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154738 - 154738

Published: Aug. 6, 2023

Language: Английский

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Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 6, 2024

Abstract Background and aims Sorafenib is a major nonsurgical option for patients with advanced hepatocellular carcinoma (HCC); however, its clinical efficacy largely undermined by the acquisition of resistance. The aim this study was to identify key lncRNA involved in regulation sorafenib response HCC. Materials methods A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA) synergistic activation mediator (SAM)-pooled library applied screen regulated treatment. role identified mediating HCC examined vitro vivo. underlying mechanism delineated proteomic analysis. significance expression evaluated multiplex immunostaining on human microtissue array. Results CRISPR/Cas9 screening revealed that Linc01056 among most downregulated lncRNAs sorafenib-resistant cells. Knockdown reduced sensitivity cells sorafenib, suppressing apoptosis promoting tumour growth mice Proteomic analysis knockdown sorafenib-treated induced genes related fatty acid oxidation (FAO) while repressing glycolysis-associated genes, leading metabolic switch favouring higher intracellular energy production. FAO inhibition significantly restored sorafenib. Mechanistically, we determined PPARα critical molecule governing upon indeed, tumours Clinically, predicted optimal overall progression-free survival outcomes better response. indicated low level Conclusion Our as epigenetic regulator potential therapeutic target

Language: Английский

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Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer

Cancer Letters, Journal Year: 2018, Volume and Issue: 418, P. 185 - 195

Published: Jan. 17, 2018

Language: Английский

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Long non-coding RNAs and cervical cancer

Experimental and Molecular Pathology, Journal Year: 2018, Volume and Issue: 106, P. 7 - 16

Published: Nov. 22, 2018

Language: Английский

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Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa‐miR‐29b‐3p in pancreatic ductal adenocarcinoma

Journal of Cellular and Molecular Medicine, Journal Year: 2017, Volume and Issue: 22(1), P. 655 - 667

Published: Oct. 5, 2017

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles PDAC poorly understood. Here, we identify fundamental role for novel lincRNA, linc00511, the progression of PDAC. Linc00511 levels tissue specimens and cell lines were examined by quantitative real‐time PCR. Corresponding adjacent non‐neoplastic tissues used as controls. The function linc00511 was determined RNA interference approach vitro vivo . Fluorescence situ hybridization (FISH) to characterize expression cells. Insights mechanism competitive endogenous (ceRNAs) obtained from bioinformatic analysis, luciferase assays RIP assays. association between linc00511/hsa‐miR29b‐3p axis VEGFA verified Western blotting assay. Immunohistochemistry performed evaluate samples. aberrant up‐regulation detected patient compared with An increase indicates adverse clinical characteristics poor prognosis. Functionally, depletion cells decreased proliferation, migration, invasion endothelial tube formation. Mechanistically, could up‐regulate via its competing (ceRNA) activity on hsa‐miR‐29b‐3p. In summary, our results define an controlling tumour angiogenesis lncRNA that plays significant regulatory pathogenesis Thus, represents new prognostic biomarker predict outcome patients after surgery may serve therapeutic target treatment.

Language: Английский

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