Differentially expressed SE-lncRNAs in lung adenocarcinoma
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PROVIDER: PRJNA805532 | ENA |
REPOSITORIES: ENA
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Project description:Differentially expressed SE-lncRNAs and mRNA in colorectal cancer
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Project description:Background: Lung adenocarcinoma (LUAD) is the leading cause of deaths worldwide, and metastasis accounts for the vast majority of cancer-related deaths. Driver mutations play important roles in treatment decision making for LUAD patients, while the complicated metastatic progress cannot be explained by genetic aberrations alone. Epigenomic reprogramming is particularly notable as an important signature of the metastasis transition. However, long noncoding RNAs (lncRNAs) hijacked by super-enhancer (SE), vital regulatory elements in epigenome, remain elusive in the progression of metastasis. Methods: SE associated lncRNAs microarray was utilized to identified the dysregulated lncRNAs related to metastasis. ChIP-seq, Hi-C data analysis and luciferase reporter assay were utilized to confirm LINC01977 was hijacked by SE. In vitro and in vivo assays were applied to elucidate effects of LINC01977 on the malignancy of LUAD. Results: In this study, we identified that LINC01977, a cancer-testis lncRNA, was up-regulated in tumor, which was driven by a …kb-long SE upstream of LINC01977 and sensitive to BRD4 inhibitor. LINC01977-antisense oligonucleotides (ASO) dramatically suppresses proliferation and invasion both in vitro and in vivo. Mechanically, LINC01977 promotes phosphorylation of SMAD3 to facilitate its nuclear retention, and it also act as a scaffold to cooperate the interaction between SMAD3 and CBP/P300, the transcriptional co-activators, to regulate the downstream target gene ZEB1. Interestingly, SMAD3 also positively regulated LINC09177 transcription by binding the promoter and active elements of its SE, which was medicated by canonical TGF-β signaling secreted by M2-like tumor-associated macrophages (TAM2). We also revealed that the expression of LINC01977 was positively correlated with TAM2 infiltration especially in early stage. Additionally, stage I LUAD patients with high LIN01977 expression predicated a shorter progression-free survival (PFS). Conclusions: LINC01977 promotes the malignant progression of LUAD through facilitating the interaction between SMAD3 and CBP/P300. The upregulation of LINC01977 was medicated by super-enhancer and TAM2 infiltration, dependent on canonical TGF-β signaling. LINC01977 could be a valuable therapeutic target especially for early stage patients.
2022-08-24 | GSE196584 | GEO
Project description:To address the role of SE-lncRNAs in CRC tumorigenesis, we performed Arraystar human SE-lncRNA microarray to profile the differentially expressed SE-lncRNAs and mRNA in four CRC and paired peritumoral tissues. According to the filter criteria of Fold Change ≥ 1.5 and P-value < 0.05, a total of 55 significantly upregulated and 29 significantly downregulated SE-LncRNs were identified. These data confirmed that the expression of SE-lncRNA undergoes a change that cannot be ignored during CRC tumorigenesis. We also identified 165 (91 up- and 74 downregulated) differentially expressed mRNA between the two groups（Fold Change > 1.5 and P-value < 0.05）(Fig.1C), which provides help for us to findpotential target genes and further explore the biological function of SE-lncRNA in CRC
2020-05-22 | GSE151021 | GEO
Project description:Lung cancer is a heterogeneous disease with high mortality rate globally. Lung adenocarcinoma (ADC) is the most common histological subtype of lung cancer. Multiple studies indicate that lncRNAs emerge as a novel class of critical regulators of cancer. However, the expression of lncRNAs has not been comprehensively surveyed in ADC at a genome-wide scale. Herein we examined landscapes of the lncRNAs and their potential target genes in an integrative fashion in ADC. The differences expression level of lncRNAs and mRNA were determined by microarray. qRT-PCR was performed to validate the lncRNAs expression level in a cohort of 42 tumor tissues and adjacent normal lung tissues. R and Bioconductor were used for data analysis. TF-lncRNAs-gene networks were generated by Cytoscape software. A total of 3045 lncRNAs were differentially expressed between tumor and normal tissues (1048 up and 1997 down). The qRT-PCR of 9 lncRNAs results showed that the expression patterns of these lncRNAs were consistent with the microarray data. Meanwhile, we find NONHSAT077036 expression was associated with N classification and clinical stage. Further, we analyzed the potential co-regulatory relationship between the lncRNAs and target genes using the ‘cis’ and ‘trans’ model. In the 25 related transcription factors (TFs), our analysis in TCGA database found that patients with lower expression of POU2F2 and higher expression of TRIM28 had a shorter overall survival time, suggesting that POU2F2 and TRIM28 could be biomarkers for poor prognosis of ADC. Hence, “POU2F2-lncRNAs” “TRIM28-lncRNAs” two element networks and “POU2F2-lncRNAs-mRNAs” “TRIM28-lncRNAs-mRNAs” there element relationship tables were generated.
2017-02-01 | GSE85716 | GEO
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