RESUMEN
A major reason for treatment failure of cancer is acquisition of drug resistance. The specific mechanisms underlying hepatocellular carcinoma (HCC) chemoresistance need to be fully elucidated. lncRNAs involve in drug resistance in some cancers, however, the exact functions of lncRNA colon cancer-associated transcript 1 (CCAT1) in oxaliplatin resistance in HCC are still unknown. Our study indicated that CCAT1 promoted HCC proliferation and reduced the apoptosis induced by oxaliplatin. Knockout of CCAT1 could increased chemosensitivity in vitro and in vivo. Further study found that QKI-5 was an important mediator and blocking of QKI-5/p38 MAPK signaling pathway could enhance oxaliplatin sensitivity. In conclusions, CCAT1 promoted proliferation and oxaliplatin resistance via QKI-5/p38 MAPK signaling pathway in HCC. Targeting CCAT1 in combination with chemotherapeutics may be a promising alternative to reverse drug resistance in HCC treatment.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , MicroARNs/genética , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Proteínas de Unión al ARN/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Micro-RNAs have been reported to play crucial roles in a diversity of cellular processes such as cell proliferation, differentiation and development by regulating the expression of specific genes. They have also been shown to play vital roles in several diseases such as cancer. In the present study, we investigated the role of miR-143-3p in breast cancer. Our results showed that the expression of miR-143-3p is significantly downregulated in breast cancer cells. Upregulation of miR-143-3p inhibited the proliferation and migration of breast cancer cells. Conversely, inhibition of miR-143-3p promoted the proliferation of cancer cells. Bioinformatics analysis and other several experiments revealed MAPK7 as the potential target of miR-143-3p. Quantitative RT-PCR showed that the expression of MAPK7 correlated well with the expression of miR-143. Moreover, the inhibition of MAPK 7 in breast cancer cells abrogated the effects of miR-143 indicating that miR-143-3p-exerted effects on breast cancer are mediated by MAPK7. Takentogether, these results provide strong clues about the therapeutic potential of miR-143-3p in the treatment of breast cancer.
