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.

SUBMITTER: Ding L

PROVIDER: S-EPMC8526484 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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lncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression.

Ding Lei L Liu Taiyuan T Qu Yuan Y Kang Zhichen Z Guo Lixin L Zhang Haina H Jiang Junjie J Qu Fuling F Ge Wanbao W Zhang Shanyong S

Molecular therapy. Nucleic acids 20210826

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 t ...[more]

PMID: 34729248

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Project description:Lymph node metastasis is the main type of metastasis in esophageal squamous cell carcinoma (ESCC), especially when the primary tumor invasion depth reaches above the adventitia layer (T3 stage), the incidence of lymph node metastasis increases sharply. Abnormal expression of long non-coding RNAs (lncRNAs) has been confirmed in ESCC, but there are still many unknown connections between lncRNAs and lymph node metastasis. We used transcriptome sequencing (RNA-seq) to analyze 10 pairs of ESCC tissues with primary tumor stage T3 and their paired normal epithelium. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to further verify the sequencing results, and survival curve analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used to investigate its clinical application value. We investigated the growth and metastasis effects of lncRNA GAS6-AS1 on ESCC cell lines TE-1 and KYSE410 in vitro and in vivo. Other functional experiments included cell apoptosis and cell cycle experiments. Based on our RNA-seq data, lncRNA GAS6-AS1 is highly expressed in ESCC tissues, especially in cancer tissues with lymph node metastasis. The qRT-PCR experiment analysis showed that high expression of GAS6-AS1 was related to poor tumor differentiation and tumor stage. Logistic regression analysis showed that it was an independent risk factor for lymph node metastasis, and ROC analysis validated that it could predict lymph node metastasis. Further survival analysis suggested that high expression of GAS6-AS1 was associated with patients' poor prognosis. In vitro experiments, knocking down GAS6-AS1 inhibited the growth and metastasis of ESCC cells and inhibited tumor growth in vivo. In addition, knocking down GAS6-AS1 can inhibit cell cycle and promote cell apoptosis. Our results revealed that lncRNA GAS6-AS1 obtained from RNA-seq can be used as an independent risk factor for ESCC lymph node metastasis and an effective biomarker to predict, and that it was related to the growth and metastasis of ESCC. It may represent a new biomarker to aid in the assessment of the lymph node metastasis of ESCC.

Dataset Information

LncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression.

Publications

lncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression.

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