In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor

Hong, Hui; Yao, Shun; Zhang, Y; Ye, Yi; Li, Cheng; Hu, Liang; Sun, Yihua; Huang, Hsin‐Yi; Ji, Hongbin

doi:10.1371/journal.pgen.1009168

Cited by 20 publications

(22 citation statements)

References 47 publications

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“…We then further investigated the regulatory relationship between CLU and associated enhancers. Using dual gRNA CRISPR system [ 57 ], we successfully performed knockout of a GI-specific enhancer, which contains the binding motif of GI core regulator HLF , in CRL-5872 cells (Fig. 5 m, n).…”

Section: Resultsmentioning

confidence: 99%

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

Yuan

Chen

et al. 2021

Genome Biol

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Background Lung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression. Results A high intertumoral epigenetic heterogeneity is observed across the LUAD H3K27ac profiles. We quantitatively model the intertumoral variability of H3K27ac levels at proximal gene promoters and distal enhancers and propose a new epigenetic classification of LUAD patients. Our classification defines two LUAD subgroups which are highly related to histological subtypes. Group II patients have significantly worse prognosis than group I, which is further confirmed in the public TCGA-LUAD cohort. Differential RNA-seq analysis between group I and group II groups reveals that those genes upregulated in group II group tend to promote cell proliferation and induce cell de-differentiation. We construct the gene co-expression networks and identify group-specific core regulators. Most of these core regulators are linked with group-specific regulatory elements, such as super-enhancers. We further show that CLU is regulated by 3 group I-specific core regulators and works as a novel tumor suppressor in LUAD. Conclusions Our study systematically characterizes the epigenetic alterations during LUAD progression and provides a new classification model that is helpful for predicting patient prognosis.

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Section: Resultsmentioning

confidence: 99%

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

Yuan

Chen

et al. 2021

Genome Biol

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“…Five downregulated DEMs (miR-578, miR-142-3p, miR-375, miR-190b and miR-609) were continuously changed in the three datasets and were identi ed as candidate DEMs for further analysis. Among them, miR-578 and miR-190b are key regulators of tumor development [16][17][18]. MiR-142-3p was downregulated in H 2 O 2 -stimulated cardiomyo-cytes in vitro and ischemia-reperfusion injured heart tissues in vivo.…”

Section: Discussionmentioning

confidence: 99%

Construction of Potential miRNA-mRNA Regulatory Network in AMI Plasma by Bioinformatics Analysis

Yang

Gao

Meng

et al. 2022

Preprint

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Background: Acute myocardial infarction (AMI) has become the main cause of incidence rate and mortality worldwide. More and more evidences indicate that abnormally expressed microRNAs (miRNAs) are involved in the pathogenesis of AMI. However, comprehensive studies on miRNA-mRNA regulatory networks in AMI plasma are still lacking.Results: In the above three datasets, a total of 5 DEMs with downregulated expression were screened. Sp1 and EGR1 may regulate most down regulated DEM. 1074 downstream target genes were predicted. The predicted target genes of DEM were mainly enriched in PI3K/Akt signal pathway, mTOR signal pathway, Hippo signal pathway, AMPK signal pathway and HIF-1 signal pathway. By constructing DEM-hub gene network, it was found that most hub genes may be regulated by miR-142-3p, miR-375 and miR-190b. Among the top 10 hub genes, the expression of STAT3 and PTEN was consistent with that in GSE66360 dataset.Conclusion: This study constructed a potential miRNA-mRNA regulatory network in the blood of AMI for the first time, which provides a new perspective for the Pathogenesis and treatment of AMI.

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“…Generally, miR-375 acts as tumor suppressor, repressing many critical oncogenes such as PDK1, JAK2, IGF1R, and AEG-1 [ 34 ]. Less known, is miR-190b, although it is also engaged in promoting many cancers such as bladder carcinoma [ 35 ] or colorectal cancer [ 36 ] and found, as well, as a novel tumor suppressor in lung cancer during in vivo miRNA knockout screening [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer

et al. 2021

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Endometrial cancer (EC) is treated according to the stage and prognostic risk factors. Most EC patients are in the early stages and they are treated surgically. However, some of them, including those with high grade (grade 3) are in the intermediate and high intermediate prognostic risk groups and may require adjuvant therapy. The goal of the study was to find differences between grades based on an miRNA gene expression profile. Tumor samples from 24 patients with grade 1 (n = 10), 2 (n = 7), and 3 (n = 7) EC were subjected to miRNA profiling using next generation sequencing. The results obtained were validated using the miRNA profile of 407 EC tumors from the external Cancer Genome Atlas (TCGA) cohort. We obtained sets of differentially expressed (DE) miRNAs with the largest amount between G2 to G1 (50 transcripts) and G3 to G1 (40 transcripts) patients. Validation of our results with external data (TCGA) gave us a reasonable gene overlap of which we selected two miRNAs (miR-375 and miR190b) that distinguish the high grade best from the low grade EC. Unsupervised clustering showed a high degree of heterogeneity within grade 2 samples. MiR-375 as well as 190b might be useful to create grading verification test for high grade EC. One of the possible mechanisms that is responsible for the high grade is modulation by virus of host morphology or physiology.

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In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor

Cited by 20 publications

References 47 publications

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

A systematic dissection of the epigenomic heterogeneity of lung adenocarcinoma reveals two different subclasses with distinct prognosis and core regulatory networks

Construction of Potential miRNA-mRNA Regulatory Network in AMI Plasma by Bioinformatics Analysis

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer

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