RESUMO
None.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Neoplasias Colorretais , Humanos , Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Terapia de Alvo MolecularRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) are closely associated with the pathogenesis of numerous diseases including cancers. LncRNA AGAP2 Antisense RNA 1 (AGAP2-AS1) has been found to participate in the tumorigenesis of several kinds of human cancers. Nonetheless, its potential function in colorectal cancer (CRC) was still poorly investigated. METHODS: The expression level of RNAs or proteins was assessed by RT-qPCR or western blot analysis. Functional experiments were performed to analyze the role of AGAP2-AS1 in CRC in vitro and in vivo. Mechanism investigations were fulfilled to determine the potential mechanism of the molecules. RESULTS: AGAP2-AS1 expression was significantly elevated in CRC cells and could be transcriptionally activated by E2F Transcription Factor 4 (E2F4). Down-regulated AGAP2-AS1 could weaken CRC cell growth, migration, invasion, and epithelial-mesenchymal transition (EMT). MicroRNA-182-5p (miR-182-5p) was the target downstream molecule of AGAP2-AS1. Furthermore, Cofilin 1 (CFL1) was proved as the target of miR-182-5p. Mechanically, AGAP2-AS1 could boost the CFL1 expression via competitively binding to miR-182-5p in CRC. Importantly, CFL1 restoration could counteract the in vitro and in vivo suppression of depleted AGAP2-AS1 on CRC progression. CONCLUSION: E2F4-stimulated AGAP2-AS1 aggravated CRC development through regulating miR-182-5p/CFL1 axis, implying that AGAP2-AS1 might become a potent new target for future therapies for CRC.
Assuntos
Neoplasias Colorretais , Proteínas de Ligação ao GTP/genética , Proteínas Ativadoras de GTPase/genética , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cofilina 1/genética , Cofilina 1/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fator de Transcrição E2F4/genética , Fator de Transcrição E2F4/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação para CimaRESUMO
INTRODUCTION: Taurine up-regulated 1 (TUG1) was reported to be over-expressed and involved in various human malignancies. However, its expression status and mechanistic importance in colorectal cancer (CRC) were yet to be defined. METHODS: Relative expressions of TUG1, miR-153-1 and Kruppel-like factor 4 (KLF4) were analyzed by real-time PCR. The potential influences of TUG1-proficiency and miR-153-1-deficiency on cell proliferation, migration and viability were determined by colony formation, wound healing and CCK-8 assays, respectively. Cell invasion was evaluated by transwell chamber assay. The regulatory effect of KLF4 on miR-153-1 was interrogated by luciferase reporter assay. Direct association between KLF4 and miR-153-1 promoter was measured by chromatin immunoprecipitation (ChIP) assay. Subcellular localization of TUG1 was determined by fractionization PCR. Enrichment of EZH2 on KLF4 promoter was analyzed by ChIP-PCR. The pro-tumoral activity of TUG1 was determined using xenograft tumor model. RESULTS: We demonstrated the over-expression of TUG1 and down-regulation of miR-153-1 in CRC. Knockdown of TUG1 or ectopic over-expression of miR-153-1 in SW480 significantly suppressed cell proliferation, migration and viability. TUG1 negatively modulated miR-153-1 expression, and simultaneous expression of TUG1 completely abolished the anti-tumor effect of miR-153-1. We further identified KLF4 as a transcription factor of miR-153-1, which was negatively regulated by TUG1 along with EZH2. CONCLUSION: Our study unravels the critical involvement of TUG1/KLF4/miR-153-1 axis in CRC.
RESUMO
Hepatocellular carcinoma (HCC) remains the fifth most frequent cancer with high mortality rate worldwide. However, the underlying molecular mechanisms of HCC progression are still barely known. Long noncoding RNAs (lncRNAs) have been recognized as significant therapeutic targets for HCC. Recently, the biological role of LINC00857 in several cancer types has been reported. Our present study was aimed to investigate the role of LINC00857 in HCC progression. We observed that LINC00857 was overexpressed in HCC cell lines (Huh7, Hep3B, HepG2, MHCC-97H, and SNU449). Knockdown of LINC00857 significantly repressed Hep-3B and SNU449 cell proliferation and inhibited the HCC cell colony formation. In addition, cell apoptosis was induced by the silence of LINC00857 and cell cycle progression was blocked in G1 phase. Besides these, downregulation of LINC00857 was able to restrain HCC cell migration and invasion capacity via enhancing epithelial-mesenchymal transition (EMT) process. As displayed, E-cadherin protein expression was increased by LINC00857 silence, while N-cadherin protein level was repressed by LV-shLINC00857 in HCC cells. Finally, the in vivo assays were used and the data indicated that LINC00857 could also obviously suppress the HCC tumor growth in vivo. In conclusion, our study revealed that LINC00857 might provide a novel perspective for the HCC treatment.