Identification and characterization of functional long noncoding RNAs in cancer

Olivero, Christiane; Dimitrova, Nadya

doi:10.1096/fj.202001951r

Cited by 20 publications

(10 citation statements)

References 171 publications

(363 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, abnormal expression of lncRNAs has been found to play a very important role in tumorigenesis and tumor progression. The study of new lncRNAs can also reveal a new mechanism of tumor development ( Sun et al, 2020 ; Olivero & Dimitrova, 2020 ; Zhang et al, 2021b ). Therefore, the exploration of new lncRNAs and the study of their biological functions will provide important impetus for tumor research.…”

Section: Discussionmentioning

confidence: 99%

High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression

Zhu¹,

Pei

J³

et al. 2023

PeerJ

View full text Add to dashboard Cite

Aims To screen abnormal lncRNAs and diagnostic biomarkers in the progression of hepatocellular carcinoma through high-throughput sequencing and explore the underlying mechanisms of abnormal lncRNAs in the progression of hepatocellular carcinoma. Methods The transcriptome sequencing was used to analyze the RNA expression profile and identify differentially expressed RNAs. Hub lncRNAs were screened by combining (WGCNA, ceRNA regulatory network, PPI, GO and KEGG analyses, Kaplan-Meier curve analysis, Cox analysis, risk model construction and qPCR). Thereafter, the correlation between the expression of hub lncRNAs and tumor clinicopathological parameters was analyzed, and the hub lncRNAs were analyzed by GSEA. Finally, the effects of hub RNAs on the proliferation, migration and invasion of HepG2 cells were investigated in vitro. Results Compared with the control group, a total of 610 lncRNAs, 2,593 mRNAs and 26 miRNAs were screened in patients with hepatocellular carcinoma. Through miRNA target prediction and WGCNA, a ceRNA was constructed, comprising 324 nodes and 621 edges. Enrichment analysis showed that mRNAs in ceRNA were involved mainly in cancer development progression. Then, the ZFAS1/miR-150-5p interaction pair was screened out by Kaplan Meier curve analysis, Cox analysis and qPCR analysis. Its expression was related to tumor stage, TNM stage and patient age. ROC curve analysis showed that it has a good predictive value for the risk of hepatocellular carcinoma. GSEA showed that ZFAS1 was also enriched in the regulation of immune response, cell differentiation and proliferation. Loss-of-function experiments revealed that ZFAS1 inhibition could remarkably suppress HepG2 cell proliferation, migration and invasion in vitro. Bioinformatic analysis and luciferase reporter assays revealed that ZFAS1 directly interacted with miR-150-5p. Rescue experiments showed that a miR-150-5p inhibitor reversed the cell proliferation, migration and invasion functions of ZFAS1 knockdown in vitro. Conclusion ZFAS1 is associated with the malignant status and prognosis of patients with hepatocellular carcinoma, and the ZFAS1/miR-150-5p axis is involved in hepatocellular carcinoma progression.

show abstract

Section: Discussionmentioning

confidence: 99%

High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression

Zhu¹,

Pei

J³

et al. 2023

PeerJ

View full text Add to dashboard Cite

show abstract

“…While protein-coding determinants of metastatic cancer have been extensively studied, lncRNAs that contribute to metastatic progression are less well characterized and frequently lack experimental validation in relevant cancer models (Olivero and Dimitrova, 2020). In this study, we present conclusive evidence that the lncRNA Malat1 is a bona fide proto-oncogene and that Malat1 overexpression is sufficient to overcome the barrier to metastatic progression in the KP mouse model of LUAD.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro CRISPRa experiments were performed with a previously described lentiviral vector (lenti-SAM-Hygro (Olivero et al, 2020)). In vitro CRISPRi experiments were performed with a lentiviral vector (lenti-KRAB-Hygro) constructed to co-express a U6-driven 15-mer ʻdead RNAʼ (dRNA) extended by two MS2 loops (dRNA-MS2), the transcriptional repressor KRAB (Kruppelassociated Box) fused to the MS2-binding protein (MBP), and a hygromycin-resistance gene.…”

Section: Constructsmentioning

confidence: 99%

“…Identification and functional characterization of long noncoding RNAs (lncRNAs) has suggested a potential wealth of unexplored cancer targets (Olivero and Dimitrova, 2020). While lncRNAs are rarely subject to recurrent mutations in cancer (Rheinbay et al, 2020), lncRNAs are frequently expressed at aberrant levels in tumors compared to normal tissues (Gutschner and Diederichs, 2012; Yan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

OverexpressedMalat1Drives Metastasis through Inflammatory Reprogramming of Lung Adenocarcinoma Microenvironment

Martínez-Terroba

Miguel

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Metastasis is the main cause of cancer deaths but the molecular events leading to metastatic dissemination remain incompletely understood. Despite reports linking aberrant expression of long noncoding RNAs (lncRNAs) with increased metastatic incidence, in vivo evidence establishing driver roles for lncRNAs in metastatic progression is lacking. Here, we report that overexpression of the metastasis-associated lncRNA Malat1 (metastasis-associated lung adenocarcinoma transcript 1) in the autochthonous K-ras/p53 mouse model of lung adenocarcinoma (LUAD) is sufficient to drive cancer progression and metastatic dissemination. We show that increased expression of endogenous Malat1 RNA cooperates with p53 loss to promote widespread LUAD progression to a poorly differentiated, invasive, and metastatic disease. Mechanistically, we observe that Malat1 overexpression leads to the inappropriate transcription and paracrine secretion of the inflammatory cytokine, Ccl2, to augment the mobility of tumor and stromal cells in vitro and to trigger inflammatory responses in the tumor microenvironment in vivo. Notably, Ccl2 blockade fully reverses cellular and organismal phenotypes of Malat1 overexpression. We propose that Malat1 overexpression in advanced tumors activates Ccl2 signaling to reprogram the tumor microenvironment to an inflammatory and pro-metastatic state.

show abstract

“…The identification of recurrent cancer‐associated genetic aberrations in several lncRNA‐producing loci has raised the possibility that lncRNAs may be drivers, and not simply passengers, of cancer development (Beroukhim et al, 2010; Prensner & Chinnaiyan, 2011; Rheinbay et al, 2020). Efforts to model the recurrent genetic alterations of lncRNAs in cellular and organismal models of cancer have provided evidence that some lncRNAs are functional mediators of cancer‐relevant processes (Olivero & Dimitrova, 2020). These studies have revealed that genetic aberrations in lncRNA loci can contribute to the acquisition of cancer hallmarks, such as hyperproliferation, enhanced survival, altered metabolism, and increased metastatic dissemination (Huarte, 2015).…”

Section: Introductionmentioning

confidence: 99%

A mechanistic view of long noncoding RNAs in cancer

Winkler

Dimitrova

2021

WIREs RNA

Self Cite

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) have emerged as important modulators of a wide range of biological processes in normal and disease states. In particular, lncRNAs have garnered significant interest as novel players in the molecular pathology of cancer, spurring efforts to define the functions, and elucidate the mechanisms through which cancer‐associated lncRNAs operate. In this review, we discuss the prevalent mechanisms employed by lncRNAs, with a critical assessment of the methodologies used to determine each molecular function. We survey the abilities of cancer‐associated lncRNAs to enact diverse trans functions throughout the nucleus and in the cytoplasm and examine the local roles of cis‐acting lncRNAs in modulating the expression of neighboring genes. In linking lncRNA functions and mechanisms to their roles in cancer biology, we contend that a detailed molecular understanding of lncRNA functionality is key to elucidating their contributions to tumorigenesis and to unlocking their therapeutic potential. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease

show abstract

Identification and characterization of functional long noncoding RNAs in cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 20 publications

References 171 publications

High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression

High-throughput sequencing approach for the identification of lncRNA biomarkers in hepatocellular carcinoma and revealing the effect of ZFAS1/miR-150-5p on hepatocellular carcinoma progression

OverexpressedMalat1Drives Metastasis through Inflammatory Reprogramming of Lung Adenocarcinoma Microenvironment

A mechanistic view of long noncoding RNAs in cancer

Contact Info

Product

Resources

About