RESUMO
Hepatocellular carcinoma (HCC) remains the most common malignant tumor worldwide. Long noncoding RNAs can modulate various tumorigenic processes. In addition, growing evidence has indicated tha the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is activated in multiple cancers, including HCC. Recently, it was found that LINC00346 can participate in several cancers. Nevertheless, the biological roles of LINC00346 in HCC have been barely investigated. In this study, the function of LINC00346 was specifically concentrated upon. We observed that LINC00346 was obviously elevated in HCC cells (Bel7404, Huh-6, HepG2, and QGY-7703 cells). Then, Bel7404 and HepG2 cells were overexpressed with LINC00346. Overexpression of LINC00346 repressed HCC cell survival and cell proliferation. In addition, apoptosis of Bel7404 and HepG2 cells was triggered by LINC00346 upregulation. Bel7404 and HepG2 cell cycle was arrested in the G1 phase by LINC00346. Meanwhile, we conducted wound-healing assay and Transwell invasion assays. As shown, we observed that the migratory and invasive capacities of Bel7404 and HepG2 cells were remarkably restrained by the increase of LINC00346. Moreover, we showed that LINC00346 overexpression activated the JAK-STAT3 pathway, which is involved in many cancers. Afterward, in vivo experiments were utilized and we proved that LINC00346 was able to induce HCC tumor growth via activating the JAK-STAT3 pathway. To conclude, we revealed the potential possibility of developing LINC00346 as an indicator for HCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Janus Quinase 1/metabolismo , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Humanos , Janus Quinase 1/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Fator de Transcrição STAT3/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent evidences have demonstrated that long non-coding RNAs (lncRNAs) act as key regulators of tumor development and progression including HCC. In the study, we showed that the expression level of HNF1A-AS1 was up-regulated in HCC cell lines. Furthermore, CCK-8 cell proliferation assays and cell cycle analysis showed that HNF1A-AS1 over-expression facilitated HCC cell proliferation by promoting the cell proliferation and S-phase progression, whereas HNF1A-AS1 knockdown had the opposite effect. Western-blotting analysis revealed that knockdown of HNF1A-AS1 inhibited the cycle-relative protein cyclin-D1 and PCNA expression in HCC cells. Mechanism, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed that by interacting with enhancer of zeste homolog 2 (EZH2), HNF1A-AS1 promoted HCC cell proliferation by repressing the NKD1 and p21 expression. These results suggested that HNF1A-AS1 may contribute to HCC progression, which may be an effective therapeutic target for patients.