A novel lncRNA, LUADT1 promotes lung adenocarcinoma proliferation by epigenetic suppression of p27
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66654 | GEO | 2015/03/10
SECONDARY ACCESSION(S): PRJNA277627
REPOSITORIES: GEO
Similar Datasets
Project description:Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers, however, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Understanding the expression profile of lncRNAs and protein-coding genes is critical to develop new diagnosis and treatment strategies for LUAD and improving the prognosis of diagnosed patients. Five female LUAD patients with no smoking history were selected to profile lncRNA and protein-coding gene expression with microarrays. Paired tumor tissues and adjacent nontumor tissues were collected and confirmed by pathologists.
2015-03-10 | E-GEOD-66654 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers, however, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Understanding the expression profile of lncRNAs and protein-coding genes is critical to develop new diagnosis and treatment strategies for LUAD and improving the prognosis of diagnosed patients. Five female LUAD patients with no smoking history were selected to profile lncRNA and protein-coding gene expression with microarrays. Paired tumor tissues and adjacent nontumor tissues were collected and confirmed by pathologists.
| S-ECPF-GEOD-66654 | biostudies-other
Project description:Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers. However, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Here, we identified the expression profile of lncRNAs and protein-coding genes via microarrays analysis of paired LUAD tissues and adjacent non-tumor tissues from five female non-smokes with LUAD. A total of 498 lncRNAs and 1691 protein-coding genes were differentially expressed between LUAD tissues and paired adjacent normal tissues. A novel lncRNA, LUAD transcript 1 (LUADT1), which is highly expressed in LUAD and correlates with T stage, was characterized. Both in vitro and in vivo data showed that LUADT1 knockdown significantly inhibited proliferation of LUAD cells and induced cell cycle arrest at the G0-G1 phase. Further analysis indicated that LUADT1 may regulate cell cycle progression by epigenetically inhibiting the expression of p27. RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that LUADT1 binds to SUZ12, a core component of polycomb repressive complex 2, and mediates the trimethylation of H3K27 at the promoter region of p27. The negative correlation between LUADT1 and p27 expression was confirmed in LUAD tissue samples. These data suggested that a set of lncRNAs and protein-coding genes were differentially expressed in LUAD. LUADT1 is an oncogenic lncRNA that regulates LUAD progression, suggesting that dysregulated lncRNAs may serve as key regulatory factors in LUAD progression.
| S-EPMC4558496 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with limited protein coding potential. Long non-coding RNAs (lncRNAs) play an important role in lung adenocarcinoma (LUAD) metastasis. In this study, we profiled matched tissue from LUAD patients with HTA 2.0 microarray analysis and identified lncRNA- chromatin-associated RNA 10 (CAR10) as obviously clearly overexpressed in LUAD tissues. we demonstrated that CAR10 accelerates tumor growth and promotes metastasis in lung adenocarcinoma. CAR10 was shown to promote epithelial-to-mesenchymal transition (EMT) translation of LUAD cells through sponging miR-30/203, leading to upregulation of SNAI1/2 expression.
2020-10-17 | GSE121397 | GEO
Project description:Although the expression of some long noncoding RNAs (lncRNAs), including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), is predictive of metastasis, their impact and mechanism of action remain elusive. Here we use CRISPR activation (CRISPRa) to model MALAT1/Malat1 overexpression in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. The results indicate that Malat1 overexpression alone is sufficient to enable the progression of LUAD to metastatic disease. We show that overexpressed MALAT1/Malat1 enhances cell mobility and promotes the recruitment of pro-tumor macrophages to the tumor microenvironment through paracrine secretion of the CCL2/Ccl2 cytokine. We determine that Ccl2 upregulation results from an increase in global chromatin accessibility upon Malat1 overexpression. Importantly, macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.
2024-10-23 | GSE265872 | GEO
Project description:Although the expression of some long noncoding RNAs (lncRNAs), including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), is predictive of metastasis, their impact and mechanism of action remain elusive. Here we use CRISPR activation (CRISPRa) to model MALAT1/Malat1 overexpression in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. The results indicate that Malat1 overexpression alone is sufficient to enable the progression of LUAD to metastatic disease. We show that overexpressed MALAT1/Malat1 enhances cell mobility and promotes the recruitment of pro-tumor macrophages to the tumor microenvironment through paracrine secretion of the CCL2/Ccl2 cytokine. We determine that Ccl2 upregulation results from an increase in global chromatin accessibility upon Malat1 overexpression. Importantly, macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.
2024-05-08 | GSE266561 | GEO
Project description:Although the expression of some long noncoding RNAs (lncRNAs), including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), is predictive of metastasis, their impact and mechanism of action remain elusive. Here we use CRISPR activation (CRISPRa) to model MALAT1/Malat1 overexpression in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. The results indicate that Malat1 overexpression alone is sufficient to enable the progression of LUAD to metastatic disease. We show that overexpressed MALAT1/Malat1 enhances cell mobility and promotes the recruitment of pro-tumor macrophages to the tumor microenvironment through paracrine secretion of the CCL2/Ccl2 cytokine. We determine that Ccl2 upregulation results from an increase in global chromatin accessibility upon Malat1 overexpression. Importantly, macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.
2024-10-26 | GSE266323 | GEO
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:Brain metastasis developed in nearly 40% of lung adenocarcinoma (LUAD) patients diagnosed with distant metastasis. There is lack of transcriptomic data of brain lesions from human lung adenocarcinoma patients. As part of the project to understanding the tumor microenvironment in brain metastasis of LUAD patients, we performed bulk RNA analysis on brain metastases from 6 LUAD patients. In order to understand the tumor intrinsic factors that potential shape the tumor microenvironment, we compared these data with bulk RNA sequencing data from 14 early stage and 11 late stage primary LUAD tumor from TCGA database. Pathway expression analysis showed a downregulation of pro-inflammatory signals in brain metastasis and upregulation of DNA synthesis and oxidative phosphorylation pathways related to rapid proliferation in brain lesions.
2019-12-10 | GSE141685 | GEO
Project description:We found lncRNA RP3-340N1.2 is highly expressed in LUAD and relatived with the progression of LUAD through high-throughput sequencing. Our results showed that the expression level of RP3-340N1.2 was upregulated significantly in three LUAD cell lines (A549, NCI_x001E_H1299, and NCI-H1975) and lentivirus-mediated knockdown of RP3-340N1.2 inhibited the differentiation, proliferation, migration, invasion, cell cycle, and other biological processes of tumor cells significantly. Bioinformatic software predicted the downstream target of RP3-340N1.2, which was verified using dual luciferase assays and other methods. We found that RP3-340N1.2 can competitively bind miR-134-5p in LUAD, and this microRNA has a significant regulatory effect on the expression of epidermal growth factor receptor (EGFR), which leads to increased migration and invasion of LUAD cells. This discovery provided a possible mechanism by which RP3-340N1.2 participates in the development of LUAD. In conclusion, our results showed that lncRNA RP3_x001E_340N1.2 regulates the expression of EGFR indirectly by targeting miR-134-5p and promotes the progression of LUAD. Therefore, RP3-340N1.2 may become a valuable biomarker and therapeutic target in LUAD.
2023-12-01 | GSE190461 | GEO