Dataset Information

Long Non-coding RNA HOTAIR Function as a Competing Endogenous RNA for miR-149-5p to Promote the Cell Growth, Migration, and Invasion in Non-small Cell Lung Cancer.

ABSTRACT: Lung cancer is a leading cause of cancer death all around the world. Long non-coding RNAs (lncRNAs) have been confirmed to be involved in carcinogenesis of malignancies. However, the molecular mechanism of most lncRNAs in various kinds of cancers remains unclear. LncRNA HOTAIR and HNRNPA1 are reported to play an oncogenic role in non-small cell lung cancer, and the overexpression of HNRNPA1 is shown to promote the proliferation of lung adenocarcinoma cells. In our study, we find that the overexpression of HOTAIR could promote the proliferation and overexpression of miR-149-5p could inhibit the proliferation of lung cancer cells. Flow cytometric analysis determines that overexpression of miR-149-5p induces cell cycle arrest in the G0/G1 phases, whereas overexpression of HOTAIR decreases the proportion of G0/G1phase cells. Also, overexpression of HOTAIR promotes the migration and invasion ability of lung cancer cells, confirmed by the wound-healing and transwell assays, which are suppressed by overexpression of miR-149-5p. Furthermore, the dual-luciferase reporter assay indicates that miR-149-5p could bind both HOTAIR and the 3'UTR of HNRNPA1. In summary, we find that HOTAIR can regulate HNRNPA1 expression through a ceRNA mechanism by sequester miR-149-5p, which post-transcriptionally targets HNRNPA1, thus promoting lung cancer progression.

SUBMITTER: Li H

PROVIDER: S-EPMC7545358 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long Non-coding RNA HOTAIR Function as a Competing Endogenous RNA for miR-149-5p to Promote the Cell Growth, Migration, and Invasion in Non-small Cell Lung Cancer.

Li Hang H Cui Zhigang Z Lv Xiaoting X Li Juan J Gao Min M Yang Zitai Z Bi Yanhong Y Zhang Ziwei Z Wang Shengli S Li Sixuan S Zhou Baosen B Yin Zhihua Z

Frontiers in oncology 20200925

Lung cancer is a leading cause of cancer death all around the world. Long non-coding RNAs (lncRNAs) have been confirmed to be involved in carcinogenesis of malignancies. However, the molecular mechanism of most lncRNAs in various kinds of cancers remains unclear. LncRNA HOTAIR and HNRNPA1 are reported to play an oncogenic role in non-small cell lung cancer, and the overexpression of HNRNPA1 is shown to promote the proliferation of lung adenocarcinoma cells. In our study, we find that the overexp ...[more]

PMID: 33102210

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Project description:Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein-protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.

Project description:BackgroundThis study aimed to develop multi-RNA-based models using a competing endogenous RNA (ceRNA) regulatory network to provide survival risk prediction in head and neck squamous cell carcinoma (HNSCC).MethodsAll long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA expression data and clinicopathological features related to HNSCC were derived from The Cancer Genome Atlas. Differentially expressed RNAs were calculated using R. Prognostic factors were identified using univariate Cox regression analysis. Functional analysis was performed using GO, KEGG pathways, and PPI network. Based on the results, we derived a risk signature and compared high- and low-risk subgroups using LASSO regression analysis. Survival analysis and the relationship between risk signature and clinicopathological features were performed using log-rank tests and Cox regression analysis. A ceRNA regulatory network was constructed, and prognostic lncRNAs and miRNA expression levels were validated in vitro and in vivo.ResultsA list of 207 lncRNAs, 18 miRNAs and 362 mRNAs related to overall survival was established. Five lncRNAs (HOTTIP, LINC00460, RMST, SFTA1P, and TM4SF19-AS1), one miRNA (hsa-miR-206), and one mRNA (STC2) were used to construct the ceRNA network. Three prognostic models contained 13 lncRNAs, eight miRNAs, and 17 mRNAs, which correlated with the patient status, disease-free survival (DFS), stage, grade, T stage, N stage, TP53 mutation status, angiolymphatic invasion, HPV status, and extracapsular spread. KEGG pathway analysis revealed significant enrichment of "Transcriptional misregulation in cancer" and "Neuroactive ligand-receptor interaction." In addition, HOTTIP, LINC00460, miR-206 and STC2 were validated in GTEx data, GEO microarrays and six HNSCC cell lines.ConclusionsOur findings clarify the interaction of ceRNA regulatory networks and crucial clinicopathological features. These results show that prognostic biomarkers can be identified by constructing multi-RNA-based prognostic models, which can be used for survival risk prediction in patients with HNSCC.

Dataset Information

Long Non-coding RNA HOTAIR Function as a Competing Endogenous RNA for miR-149-5p to Promote the Cell Growth, Migration, and Invasion in Non-small Cell Lung Cancer.

Publications

Long Non-coding RNA HOTAIR Function as a Competing Endogenous RNA for miR-149-5p to Promote the Cell Growth, Migration, and Invasion in Non-small Cell Lung Cancer.

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