Long non-coding RNA CAR10 promotes lung adenocarcinoma metastasis via miR-203/30/SNAI axis
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ABSTRACT:
PROVIDER: PRJNA497258 | ENA |
REPOSITORIES: ENA
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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:Long noncoding RNAs (lncRNAs) play an important role in lung adenocarcinoma (LUAD) metastasis. Here, we found that lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis in vitro and in vivo. Mechanistically, CAR10 induced epithelial-to-mesenchymal transition (EMT) by directly binding with miR-30 and miR-203 and then regulating the expression of SNAI1 and SNAI2. CAR10 overexpression was positively correlated with a poor prognosis in LUAD patients, whereas overexpression of both CAR10 and SNAI was correlated with even worse clinical outcomes. In conclusion, the CAR10/miR-30/203/SNAI axis is a novel and potential therapeutic target for LUAD.
| S-EPMC6484688 | biostudies-literature
Project description:Introduction: Transforming growth factor-beta (TGFβ) signaling plays a vital role in lung adenocarcinoma (LUAD) progression. However, the involvement of TGFβ-regulated long non-coding RNAs (lncRNAs) in metastasis of LUAD remains poorly understood. Methods: We performed bioinformatic analyses to identify putative lncRNAs regulated by TGF-β/SMAD3 and validated the results by quantitative PCR in LUAD cells. We performed luciferase reporter and chromatin immunoprecipitation assays to demonstrate the transcriptional regulation of the lncRNA histocompatibility leukocyte antigen complex P5 (HCP5) we decided to focus on. Stable HCP5 knockdown and HCP5-overexpressing A549 cell variants were generated respectively, to study HCP5 function and understand its mechanism of action. We also confirmed our findings in mouse xenografts and metastasis models. We analyzed the correlation between the level of lncRNA expression with EGFR, KRAS mutations, smoke state and prognostic of LUAD patients. Results: We found that the lncRNA HCP5 is induced by TGFβ and transcriptionally regulated by SMAD3, which promotes LUAD tumor growth and metastasis. Moreover, HCP5 is overexpressed in tumor tissues of patients with LUAD, specifically in patients with EGFR and KRAS mutations and current smoker. HCP5 high expression level is positively correlated with poor prognosis of patients with LUAD. Finally, we demonstrated that upregulation of HCP5 increases the expression of Snail and Slug by sponging the microRNA-203 (miR-203) and promoting epithelial-mesenchymal transition (EMT) in LUAD cells. Conclusions: Our work demonstrates that the lncRNA HCP5 is transcriptionally regulated by SMAD3 and acts as a new regulator in the TGFβ/SMAD signaling pathway. Therefore, HCP5 can serve as a potential therapeutic target in LUAD.
| S-EPMC6525996 | biostudies-literature
Project description:Purpose: identification of mRNAs that are potential targets of miR-203 in the endometrium and endometrial carcinoma Methods: mRNA profiles of three batches of wild-type (WT) and three independently generated miR-203 knockout (miR-203 KO) RUCA-I cells were produced by deep sequencing, using Illumina HiSeq 2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. Results: Using an optimized data analysis workflow, we mapped between 30 and 50 million sequence reads per sample to the rat genome (build rn6) and identified 26751 transcripts of which 1591 are differentially expressed in WT and miR-203 KO cells (p<0.05).
2017-03-10 | GSE95850 | GEO
Project description:Investigating the functions of the proteins with no or less functional annotations is an important goal of C-HPP (Chromosome-centric Human Proteome Project). In this study, we investigated the function of such a protein, ZSWIM1 (C20orf162). Its expression is upregulated in lung adenocarcinoma compared with the adjacent normal tissues and negatively correlated with the overall survival (OS). Overexpressing ZSWIM1 markedly promotes the proliferation, migration, invasion as well as epithelial-mesenchymal transition (EMT) in lung adenocarcinoma cells, while knocking down ZSWIM1 functions oppositely. Immunoprecipitation-mass spectrometry (IP-MS) identified the interactome of ZSWIM1 and we verified the interaction of it with the top partner, STK38. ZSWIM1 antagonized the function of STK38. Mechanically, ZSWIM1 promoted the activation of MEKK2/ERK1/2 pathway through interacting with STK38, leading to the release of MEKK2. Taken together, ZSWIM1 can be annotated as an oncogene in lung adenocarcinoma, and the STK38/MEKK2/ERK1/2 axis mediates its promoting role on lung adenocarcinoma.
2023-01-04 | PXD035006 | Pride
Project description:EZH2-GATA6 axis in Pancreatic ductal adenocarcinoma
| PRJNA643152 | ENA
Project description:The colonization of distant organs by metastatic carcinoma cells underpins most human cancer-related deaths, including those from head and neck squamous cell carcinoma (HNSCC). We report that miR-203, a miRNA that promotes keratinocyte differentiation, is necessary and sufficient to inhibit multiple post-extravasation events during HNSCC lung metastasis, including initial survival/engraftment, escape from metastatic dormancy, and overt colonization in vivo. Restoration of miR-203 expression in established lung metastases reduces overall metastatic burden. Instead of promoting differentiation, miR-203 controls lung metastasis through direct targeting of genes involved in cytoskeletal dynamics (LASP1), ECM remodeling (SPARC), and cell metabolism (NUAK1). Expression of miR-203 and its downstream targets correlates with HNSCC overall survival outcomes, suggesting the therapeutic potential of targeting this signaling axis. Total RNA (including small RNAs) was isolated from cultured cells stably infected in biological duplicate with either a scrambled control hairpin or miR-203. Samples were harvested in technical duplicate.
2016-07-03 | E-GEOD-47028 | biostudies-arrayexpress
Project description:The colonization of distant organs by metastatic carcinoma cells underpins most human cancer-related deaths, including those from head and neck squamous cell carcinoma (HNSCC). We report that miR-203, a miRNA that promotes keratinocyte differentiation, is necessary and sufficient to inhibit multiple post-extravasation events during HNSCC lung metastasis, including initial survival/engraftment, escape from metastatic dormancy, and overt colonization in vivo. Restoration of miR-203 expression in established lung metastases reduces overall metastatic burden. Instead of promoting differentiation, miR-203 controls lung metastasis through direct targeting of genes involved in cytoskeletal dynamics (LASP1), ECM remodeling (SPARC), and cell metabolism (NUAK1). Expression of miR-203 and its downstream targets correlates with HNSCC overall survival outcomes, suggesting the therapeutic potential of targeting this signaling axis.
2016-01-01 | GSE47028 | GEO
Project description:To identify putative novel specific targets of miR-203-3p, we overexpressed this miRNAs in primary keratinocytes using a synthetic mimic (pre-miR-203a-3p) or a synthetic “negative” control mimic (pre-miR-ctrl). RNA samples were harvested 30 hours post-transfection and 3 independent experiments were carried out.
2023-09-06 | GSE223523 | GEO
Project description:We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA. We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203.
2013-03-14 | GSE45121 | GEO