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LncRNA HOXD-AS1 promotes the metastasis of human hepatocellular carcinoma via modulating miR-326/SLC27A4.

ABSTRACT: Background:Mounting evidences have indicated that long non-coding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) is dysregulated and participates into the progression of cancers. This study aims to investigate the biological roles and mechanisms of HOXD-AS1 in the metastasis of hepatocellular carcinoma (HCC). Methods:The quantitative real-time PCR (qPCR) assay was used to assess the level of miR-326 and HOXD-AS1 in HCC tissues and cell lines. The growth of HCC cell was analyzed by using CCK-8 assay and colony formation assay. The migration and invasion of HCC cell were investigated by using wound healing and transwell invasion analysis. The expressions of SLC27A4, N-cadherin and E-cadherin were determined by western blotting. The growth of HCC cell in vivo was assessed by using xenograft model. Results:Here, we elaborated that HOXD-AS1 was overexpressed in HCC tissues than that in the adjacent normal tissues and the level of HOXD-AS1 was related with the aggressive phenotypes of HCC. Functionally, downregulation of HOXD-AS1 repressed the proliferation, invasion abilities of HCC cell in vitro and the distant metastasis of HCC cell in vivo. Further investigations demonstrated that HOXD-AS1 directly bound with miR-326 and thereby regulated its endogenous target gene, solute carrier family 27 member 4 (SLC27A4). Conclusions:All these findings indicated that HOXD-AS1-miR-326-SLC27A4 axis participated into the progression of HCC.

SUBMITTER: Ji W

PROVIDER: S-EPMC7216491 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LncRNA HOXD-AS1 promotes the metastasis of human hepatocellular carcinoma via modulating miR-326/SLC27A4.

Ji Wenbin W Wang Qunfeng Q Yang Jian J

Cancer cell international 20200512

<h4>Background</h4>Mounting evidences have indicated that long non-coding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) is dysregulated and participates into the progression of cancers. This study aims to investigate the biological roles and mechanisms of HOXD-AS1 in the metastasis of hepatocellular carcinoma (HCC).<h4>Methods</h4>The quantitative real-time PCR (qPCR) assay was used to assess the level of miR-326 and HOXD-AS1 in HCC tissues and cell lines. The growth of HCC cell was analy ...[more]

PMID: 32425696

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Project description:GBM (Glioblastoma multiform) is the most malignant tumor type of the central nervous system and has poor diagnostic and clinical outcomes. LncRNAs (Long non-coding RNAs) have been reported to participate in multiple biological and pathological processes, but their underlying mechanism remains poorly understood. Here, we aimed to explore the role of the lncRNA HAS2-AS1 (HAS2 antisense RNA 1) in GBM. GSE103227 was analyzed, and qRT-PCR was performed to measure the expression of HAS2-AS1 in GBM. FISH (Fluorescence in situ hybridization) was performed to verify the localization of HAS2-AS1. The interaction between HAS2-AS1 and miR-137 (microRNA-137) was predicted by LncBook and miRcode followed by dual-luciferase reporter assays, and the relationships among HAS2-AS1, miR-137 and LSD1 (lysine-specific demethylase 1) were assessed by WB (western blot) and qRT-PCR. Colony formation and CCK-8 (cell counting kit-8) assays were performed as functional tests. In vivo, nude mice were used to confirm the function of HAS2-AS1. HAS2-AS1 expression was upregulated in GBM cell lines, and HAS2-AS1 was localized mainly in the cytoplasm. In vitro, high HAS2-AS1 expression promoted proliferation, and knockdown of HAS2-AS1 significantly inhibited proliferation. Furthermore, HAS2-AS1 functioned as a ceRNA (competing endogenous RNA) of miR-137, leading to the disinhibition of its downstream target LSD1. The miR-137 level was downregulated by HAS2-AS1 overexpression and upregulated by HAS2-AS1 knockdown. In a subsequent study, LSD1 expression was negatively regulated by miR-137, while miR-137 reversed the LSD1 expression levels caused by HAS2-AS1. These results were further supported by the nude mouse tumorigenesis experiment; compared with xenografts with high HAS2-AS1 expression, the group with low levels of HAS2-AS1 exhibited suppressed proliferation and better survival. We conclude that lncRNA HAS2-AS1 promotes proliferation by functioning as a miR-137 decoy to increase LSD1 levels and thus might be a possible biomarker for GBM.

Dataset Information

LncRNA HOXD-AS1 promotes the metastasis of human hepatocellular carcinoma via modulating miR-326/SLC27A4.

Publications

LncRNA HOXD-AS1 promotes the metastasis of human hepatocellular carcinoma via modulating miR-326/SLC27A4.

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