Silencing of long noncoding RNA HOXD‐AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway
| Autor: | Ying Guo, Fanpu Ji, Hongwei Tian, Jun Li, Jing Tian, Mengchen Zhu, Guangyao Kong, Jin Sun, Zongfang Li, Yi Yang, Beibei Bie |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway Carcinoma Hepatocellular MAP Kinase Kinase 1 Apoptosis Biology Biochemistry Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Cyclin D1 Cell Movement Cell Line Tumor Biomarkers Tumor Animals Humans Gene silencing Gene Silencing RNA-Seq Extracellular Signal-Regulated MAP Kinases Cyclin B1 Molecular Biology In Situ Hybridization Fluorescence Cell Proliferation Mice Inbred BALB C Cell growth Cell Cycle Liver Neoplasms Computational Biology Cell Biology Cell cycle Antisense RNA 030104 developmental biology Liver 030220 oncology & carcinogenesis Disease Progression Cancer research RNA Long Noncoding Signal Transduction |
| Zdroj: | Journal of Cellular Biochemistry. 121:443-457 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | Accumulating findings reveal that long noncoding RNAs (lncRNAs) as crucial regulatory molecules serve vital functions in the progression of hepatocellular carcinoma (HCC). This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD-AS1 was increased in HCC tissues/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD-AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. In vitro loss-of-function experiments revealed that silencing of HOXD-AS1 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-7402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL-2, BAX, and MMP2. In vivo assay also showed that HOXD-AS1 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-AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD-AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer-related 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-AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD-AS1 silencing could inhibit the MEK/ERK pathway in Bel-7402 cells. Collectively, HOXD-AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC. |
| Databáze: | OpenAIRE |
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