Dataset Information

LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972.

ABSTRACT: Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation assay, CCK-8 assay, flow cytometry, wound healing assay, transwell assay, and RT-qPCR assay and used a xenograft model to investigate the influence of LINC00588 on cell proliferation, viability, cell apoptosis and cycle, migration, invasion, endothelial cell function, EMT (epithelial to mesenchymal transition), and tumor growth, respectively. Overexpression of LINC00588 appeared to inhibit cell proliferation, viability, migration, invasion, endothelial cell function, EMT, and tumor growth but not apoptosis, while we got the opposite result when we knocked down LINC00588. Next, we predicted that LINC00588 bound to miRNA-1972 and significantly downregulated its expression, which we then verified through a luciferase reporter assay. Subsequently, we knocked down miR1972 and performed CCK-8 and transwell assays to demonstrate that downregulation of miRNA-1972 could substantially inhibit the viability and invasion of osteosarcoma cells. The expression of TP53 was downregulated at the protein level but not at the mRNA level after the overexpression of miRNA-1972. Taken together, our findings indicate that LINC00588 plays a role in OS development by downregulating the expression of miRNA-1972, which can, in turn, inhibit the expression of TP53. Hence, we believe that the LINC00588/miRNA-1072/TP53 axis could potentially serve as a therapeutic target or diagnostic biomarker for osteosarcoma.

SUBMITTER: Zhou FC

PROVIDER: S-EPMC7107012 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972.

Zhou Fu-Chao FC Zhang Yue-Hui YH Liu Hai-Tao HT Song Jia J Shao Jiang J

Frontiers in pharmacology 20200324

Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation a ...[more]

PMID: 32265694

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Project description:BackgroundLong noncoding RNAs (lncRNAs) have critical regulatory functions in biological and pathological activities during osteosarcoma progression. It is important to elucidate the expression pattern and reveal the underlying mechanisms of the newly identified lncRNAs.MethodsHerein, we screened the differentially expressed lncRNAs in osteosarcoma tumors and cell lines using lncRNA microarray. The candidate lncRNA was further verified by qRT-PCR, and the association of gene expression with clinicopathological features was evaluated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The targeting miRNA was identified using starBase analysis, and the competing endogenous RNA (ceRNA) network was established by STRING. Overexpression and silence of RNA were detected by qRT-PCR. Osteosarcoma cell proliferation was measured with CCK-8 assay, and the migration and invasion were evaluated with Transwell assay. Colony formation assay was observed. Flow cytometry evaluated the cell cycle. Western blot was performed to detect the mitotic markers and apoptosis-related proteins. A nude mouse tumor formation experiment was used to evaluate osteosarcoma progression in vivo. Cooverexpressing miR-34b-3p with RAD51 reversed the miR-34b-3p-induced changes in proliferation, the cell cycle, the expression of H2A.X, and that of apoptosis-related proteins.ResultsHCG9 was identified as osteosarcoma-associated lncRNA. Osteosarcoma tissues and cell lines expressed higher levels of HCG9 as compared to normal tissues and osteoblasts, and high expression of HCG9 was further proved to be related to metastasis and the grade of osteosarcoma in clinical cases. Knockdown of HCG9 inhibited the proliferation, migration, and invasion of osteosarcoma cells. miR-34b-3p was identified as the target of HCG9, and RAD51 acted as a potential target of miR-34b-3p. Cooverexpressing miR-34b-3p with HCG9 partially suppressed the HCG9-stimulated proliferation, migration, and invasion of osteosarcoma cells in vitro and delayed the tumor progression in vivo.ConclusionWe discovered that lncRNA HCG9 promoted the proliferation of osteosarcoma cells via suppressing miR-34b-3p. Our study provides novel biomarkers and potential therapeutic targets for osteosarcoma treatment.

Project description:Accumulating evidence has indicated that noncoding RNAs are involved in intervertebral disc degeneration (IDD); however, the competing endogenous RNA (ceRNA)‑mediated regulatory mechanisms in IDD remain rarely reported. The present study aimed to comprehensively investigate the alterations in expression levels of circular RNA (circRNA), long noncoding RNA (lncRNA), microRNA (miRNA/miR) and mRNA in the nucleus pulposus (NP) of patients with IDD. In addition, crucial lncRNA/circRNA‑miRNA‑mRNA ceRNA interaction axes were screened using the GSE67567 microarray dataset obtained from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs) or genes (DEGs) between IDD and normal controls were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for DEGs based on protein databases, followed by module analysis. The ceRNA network was constructed based on the interaction between miRNAs and mRNAs, and lncRNAs/circRNAs and miRNAs. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery database. The present study identified 636 DECs, 115 DELs, 84 DEMs and 1,040 DEGs between patients with IDD and control individuals. PPI network analysis demonstrated that Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), mitogen‑activated protein kinase 1 (MAPK1), hypoxia inducible factor 1 subunit α (HIF1A) and transforming growth factor β1 (TGFB1) were hub genes and enriched in modules. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1)/hsa_circRNA_102348‑hsa‑miR‑185‑5p‑TGFB1/FOS, MALAT1‑hsa‑miR‑155‑5p‑HIF1A, hsa_circRNA_102399‑hsa‑miR‑302a‑3p‑HIF1A, MALAT1‑hsa‑miR‑519d‑3p‑MAPK1 and hsa_circRNA_100086‑hsa‑miR‑509‑3p‑MAPK1 ceRNA axes were obtained by constructing the ceRNA networks. In conclusion, these identified ceRNA interaction axes may be crucial targets for the treatment of IDD.

Dataset Information

LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972.

Publications

LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972.

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