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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:Long noncoding RNAs (lncRNAs) have a certain link to genomic stability (GS). However, the regulatory relationship of lncRNAs and GS has not been thoroughly investigated in hepatocellular carcinoma (HCC). In the present study, samples were retrieved from The Cancer Genome Atlas with somatic mutations and lncRNA expression data. Cox regression analysis was used to identify independent prognostic factors. The RNA levels were determined by reverse transcription‑quantitative PCR and protein levels were detected by western blot analysis. Cell Counting Kit‑8 and colony‑formation assays were used to assess cell viability. Cell migration was measured by wound‑healing and Transwell assays. Cell apoptosis and cell‑cycle progression were evaluated by flow cytometry. GS was detected by alkaline comet and chromosomal aberration assays. A xenograft model and lung metastasis model were used to assess the role of zinc finger protein, FOG family member 2 antisense 1 (ZFPM2‑AS1) in tumor growth in vivo. The molecular mechanisms underlying the biological functions of ZFPM2‑AS1 were investigated through bioinformatics prediction, RNA pull‑down and luciferase reporter assays. A total of 85 genomic instability‑related lncRNAs were identified and a prognostic model was developed. The prognostic model exhibited good predictive power (area under the receiver operating characteristic curve, 0.786). ZFPM2‑AS1 was significantly upregulated in tumor tissues (P<0.001) and it promoted DNA damage repair (P<0.01) and tumor progression in vitro and in vivo. Luciferase reporter assays demonstrated that miR‑3065‑5p was able to bind directly with ZFPM2‑AS1 and X‑ray repair cross complementing 4 (XRCC4). ZFPM2‑AS1 upregulated XRCC4 expression by acting as a sponge (P<0.001). In the present study, a prognostic model for HCC was developed and validated, and one lncRNA of its components was experimentally investigated. ZFPM2‑AS1 regulates XRCC4 by sponging miR‑3065‑5p to promote GS and HCC progression.

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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