CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer

McCleland, Mark L.; Mesh, Kathryn; Lorenzana, Edward; Chopra, Vivek S.; Segal, Ehud; Watanabe, Colin; Haley, Benjamin; Mayba, Oleg; Yaylaoglu, Murat; Gnad, Florian; Firestein, Ron

doi:10.1172/jci83265

Cited by 199 publications

(179 citation statements)

References 82 publications

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“…Recently, a growing number of publications have shown that lncRNAs are deregulated in malignant tumors and participate in carcinogenesis [20, 21]. In addition, lncRNAs also modulate glioma biology, such as migration, invasion, angiogenesis, and drug resistance [10, 11, 22].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Gao

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Vasculogenic mimicry (VM) has been reported to be a novel glioma neovascularization process. Anti-VM therapy provides new insight into glioma clinical management. In this study, we revealed the role of the long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) in malignant glioma behaviors and VM formation. Methods: Quantitative real-time PCR was performed to determine the expression levels of HOXA-AS2 in glioma samples and glioblastoma cell lines. CD34-periodic acid-Schiff dual-staining was performed to assess VM in glioma samples. CCK-8, transwell, and Matrigel tube formation assays were performed to measure the effects of HOXA-AS2 knockdown on cell viability, migration, invasion, and VM tube formation, respectively. RNA immunoprecipitation, dual-luciferase reporter and Western blot assays were performed to explore the molecular mechanisms underlying the functions of HOXS-AS2 in glioblastoma cells. A nude mouse xenograft model was used to investigate the role of HOXA-AS2 in xenograft glioma growth and VM density. Student’s t-tests, one-way ANOVAs followed by Bonferroni posthoc tests, and chi-square tests were used for the statistical analyses. Results: HOXA-AS2 was upregulated in glioma samples and cell lines and was positively correlated with VM. HOXA-AS2 knockdown attenuated cell viability, migration, invasion, and VM formation in glioma cells and inhibited the expression of vascular endothelial-cadherin (VE-cadherin), as well as the expression and activity of matrix metalloproteinase matrix metalloproteinase (MMP)-2 and MMP-9. miR-373 was downregulated in glioma samples and cell lines and suppressed malignancy in glioblastoma cells. HOXA-AS2 bound to miR-373 and negatively regulated its expression. Epidermal growth factor receptor (EGFR), a target of miR-373, increased the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9, via activating phosphatidylinositol 3-kinase/serine/threonine kinase pathways. HOXA-AS2 knockdown combined with miR-373 overexpression yielded optimal tumor suppressive effects and the lowest VM density in vivo. Conclusion: HOXA-AS2 knockdown inhibited malignant glioma behaviors and VM formation via the miR-373/EGFR axis.

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Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Gao

Liu

et al. 2017

Cell Physiol Biochem

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“…An increasing amount of evidence has demonstrated that lncRNAs exhibit crucial regulatory roles in the biological processes of cancer, including genomic imprinting, chromatin modification and post-transcriptional processing (7)(8)(9)(10). Increasingly, studies have indicated that lncRNAs may be used as potential prognostic biomarkers and therapeutic targets (11,12). Gastric adenocarcinoma-associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) has been demonstrated to be aberrantly expressed in gastric and colorectal cancer (13,14).…”

Section: Introductionmentioning

confidence: 99%

Upregulated GAPLINC predicts a poor prognosis in bladder cancer patients and promotes tumor proliferation and invasion

et al. 2018

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“…Some groups have previously attempted to develop arrayed CRISPR screens (Hultquist et al 2016;McCleland et al 2016;Tan and Martin 2016;Datlinger et al 2017;Strezoska et al 2017). These studies were based on guide RNA libraries consisting of individual lentiviral sgRNAs for single genes or synthesized CRISPR RNA (crRNA) in a manner similar to siRNA screens.…”

mentioning

confidence: 99%

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection

Lee

Kim

et al. 2018

Genome Res.

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Pooled CRISPR screens based on lentiviral systems have been widely applied to identify the effect of gene knockout on cellular phenotype. Although many screens were successful, they also have the limitation that genes conferring mild phenotypes or those essential for growth can be overlooked, as every genetic perturbation is incorporated in the same population. Arrayed screens, on the other hand, incorporate a single genetic perturbation in each well and could overcome these limitations. However, arrayed screens based on siRNA-mediated knockdown were recently criticized for low reproducibility caused by incomplete inhibition of gene expression. To overcome these limitations, we developed a novel arrayed CRISPR screen based on a plasmid library expressing a single guide RNA (sgRNA) and disrupted 1514 genes, encoding kinases, proteins related to endocytosis, and Golgi-localized proteins, individually using 4542 sgRNAs (three sgRNAs per gene). This screen revealed host factors required for infection by coxsackievirus B3 (CVB3) from Picornaviridae, which includes human pathogens causing diverse diseases. Many host factors that had been overlooked in a conventional pooled screen were identified for CVB3 infection, including entry-related factors, translational initiation factors, and several replication factors with different functions, demonstrating the advantage of the arrayed screen. This screen was quite reliable and reproducible, as most genes identified in the primary screen were confirmed in secondary screens. Moreover, ACBD3, whose phenotype was not affected by siRNA-mediated knockdown, was reliably identified. We propose that arrayed CRISPR screens based on sgRNA plasmid libraries are powerful tools for arrayed genetic screening and applicable to larger-scale screens.

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CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer

Cited by 199 publications

References 82 publications

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Upregulated GAPLINC predicts a poor prognosis in bladder cancer patients and promotes tumor proliferation and invasion

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection

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