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This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD\u2010AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD\u2010AS1 was increased in HCC tissues\/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD\u2010AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. <jats:italic>In vitro<\/jats:italic> loss\u2010of\u2010function experiments revealed that silencing of HOXD\u2010AS1 could dramatically suppress the proliferation, migration, and invasion, and induce S or\/and G2\/M phase cell cycle arrest as well as apoptosis of Bel\u20107402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL\u20102, BAX, and MMP2. <jats:italic>In vivo<\/jats:italic> assay also showed that HOXD\u2010AS1 silencing could markedly reduce xenograft tumor volume and weight of HCC cells. Transcriptome and bioinformatic analysis indicated that a total of 1103 genes were significantly altered by HOXD\u2010AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD\u2010AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer\u2010related biological processes (cell proliferation, cell cycle, apoptosis, migration, angiogenesis, and hypoxic response). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that HOXD\u2010AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen\u2010activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD\u2010AS1 silencing could inhibit the MEK\/ERK pathway in Bel\u20107402 cells. Collectively, HOXD\u2010AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC.<\/jats:p>","DOI":"10.1002\/jcb.29206","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T04:20:08Z","timestamp":1561350008000},"page":"443-457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Silencing of long noncoding RNA HOXD\u2010AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK\/ERK pathway"],"prefix":"10.1002","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4332-2870","authenticated-orcid":false,"given":"Jin","family":"Sun","sequence":"first","affiliation":[{"name":"National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy The Second Affiliated Hospital of Xi'an Jiaotong University 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