Dataset Information

LncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression

ABSTRACT: Osteosarcoma is a highly aggressive cancer common in children and adolescents. There is still a lack of effective treatments for metastatic or recurrent osteosarcoma. The role of long non-coding RNAs (lncRNAs) in osteosarcoma has gradually attracted attention. Here, we identified lncRNAs that were abnormally expressed in metastatic osteosarcoma through analyzing the sequencing data of osteosarcoma tissues and selected upregulated lncRNA MELTF-AS1 for detailed study. The qRT-PCR analysis showed that the expression of MELTF-AS1 was increased in osteosarcoma tissues and cells, and the high expression of MELTF-AS1 indicated a poor prognosis of osteosarcoma patients. The high expression of MELTF-AS1 in osteosarcoma was partly due to the transcriptional activation of RREB1. The results of transwell assays, scratch wound healing assays, and the tail vein injection lung metastasis model demonstrated that knocking down MELTF-AS1 inhibited metastasis ability of osteosarcoma cells. Furthermore, the results of RNA pull-down assays, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays revealed that MELTF-AS1 could regulate MMP14 expression through interaction with miR-485-5p. Our study suggested that MELTF-AS1 functioned as a pro-metastasis gene in osteosarcoma by upregulating MMP14 and that it could be a potential therapeutic and diagnostic target for osteosarcoma. Graphical abstract lncRNAs play crucial roles in cancer metastasis. Ding et al. demonstrate that MELTF-AS1 acts as a pro-metastasis gene in osteosarcoma. They revealed that MELTF-AS1 was mainly located in cytoplasm and could increase MMP14 expression through acting as a molecular sponge for miR-485-5p.

SUBMITTER: Ding L

PROVIDER: S-EPMC8526484 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The long noncoding RNA CDKN2B-AS1 harbors a major coronary artery disease risk haplotype, which is also associated with progressive forms of the oral inflammatory disease periodontitis as well as myocardial infarction (MI). Despite extensive research, there is currently no broad consensus on the function of CDKN2B-AS1 that would explain a common molecular role of this lncRNA in these diseases. Our aim was to investigate the role of CDKN2B-AS1 in gingival cells to better understand the molecular mechanisms underlying the increased risk of progressive periodontitis. We downregulated CDKN2B-AS1 transcript levels in primary gingival fibroblasts with LNA GapmeRs. Following RNA-sequencing, we performed differential expression, gene set enrichment analyses and Western Blotting. Putative causal alleles were searched by analyzing associated DNA sequence variants for changes of predicted transcription factor binding sites. We functionally characterized putative functional alleles using luciferase-reporter and antibody electrophoretic mobility shift assays in gingival fibroblasts and HeLa cells. Of all gene sets analysed, collagen biosynthesis was most significantly upregulated (Padj=9.7 × 10- 5 (AUC > 0.65) with the CAD and MI risk gene COL4A1 showing strongest upregulation of the enriched gene sets (Fold change = 12.13, Padj = 4.9 × 10- 25). The inflammatory "TNFA signaling via NFKB" gene set was downregulated the most (Padj=1 × 10- 5 (AUC = 0.60). On the single gene level, CAPNS2, involved in extracellular matrix organization, was the top upregulated protein coding gene (Fold change = 48.5, P < 9 × 10- 24). The risk variant rs10757278 altered a binding site of the pathogen responsive transcription factor STAT1 (P = 5.8 × 10- 6). rs10757278-G allele reduced STAT1 binding 14.4% and rs10757278-A decreased luciferase activity in gingival fibroblasts 41.2% (P = 0.0056), corresponding with GTEx data. CDKN2B-AS1 represses collagen gene expression in gingival fibroblasts. Dysregulated collagen biosynthesis through allele-specific CDKN2B-AS1 expression in response to inflammatory factors may affect collagen synthesis, and in consequence tissue barrier and atherosclerotic plaque stability.

Dataset Information

LncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets