RESUMEN
Oral squamous cell carcinoma (OSCC) is aggressive accompanied with poor prognosis. We previously isolated the most invasive cells resembling the invasive tumour front by microfluidic technology and explored their differentially expressed microRNAs (miRNAs) in our previous work. Here, we verified the miR-29b-3p as a guarder that suppressed migration and invasion of OSCC cells and was down-regulated in the most invasive cells. Besides that, the invasion suppression role of miR-29b-3p was achieved through the IL32/AKT pathway. Thus, miR-29b-3p and IL32 might serve as therapeutic targets for blocking the progression and improving the outcome of OSCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Regulación Neoplásica de la Expresión Génica , Interleucinas/metabolismo , MicroARNs/genética , Neoplasias de la Boca/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Movimiento Celular , Proliferación Celular , Humanos , Interleucinas/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-akt/genética , Células Tumorales CultivadasRESUMEN
The invasion front of oral squamous cell carcinoma (OSCC) harbors the most aggressive cells of the tumor and is critical for cancer invasion and metastasis. MicroRNAs (miRNAs) play important roles in OSCC progression. In this study, we modelled the OSCC invasion front on a microfluidic chip, and investigated differences in miRNA profiles between cells in the invasion front and those in the tumor mass by small RNA sequencing. We found that miR-218-5p was downregulated in invasion front cells and negatively regulates OSCC invasiveness by targeting the CD44-ROCK pathway. Thus, miR-218-5p may serve as a useful therapeutic target for OSCC. Moreover, invasion front cell isolation based-on microfluidic technology provided a useful strategy for cancer invasion study.
Asunto(s)
Movimiento Celular , Receptores de Hialuranos/metabolismo , MicroARNs/metabolismo , Neoplasias de la Boca/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Quinasas Asociadas a rho/metabolismo , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Dispositivos Laboratorio en un Chip , MicroARNs/genética , Técnicas Analíticas Microfluídicas/instrumentación , Neoplasias de la Boca/enzimología , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Invasividad Neoplásica , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello/enzimología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factores de TiempoRESUMEN
Increasing evidence has revealed the aberrant expression of long non-coding RNAs (lncRNAs) in many cancer types, including oral squamous cell carcinoma (OSCC). However, limited investigations report metastasis-related lncRNAs in OSCC. Herein, we report the identification of dysregulated intergenic lncRNAs in the highly metastatic OSCC cell line, UM-SCC6H. One of the lncRNAs, termed AC132217.4, was remarkably upregulated and promoted cell migration and epithelial-mesenchymal transition (EMT) by upregulating IGF2 expression. Further mechanistic studies revealed that AC132217.4 interacted with the 3'UTR of IGF2 mRNA and increased its stability, leading to increased IGF2 levels. Thereafter, we found that KLF8 binds to the upstream sequence of AC132217.4, activating its expression at the transcriptional level, which accelerated OSCC metastasis via the AC132217.4-IGF2 axis both in vitro and in vivo. We also revealed that the expression level of AC132217.4 was increased in OSCC tissues, and this elevation correlated with KLF8 and IGF2 expression. Thus, our data demonstrate that the KLF8-AC132217.4-IGF2 signalling pathway plays a critical role in OSCC metastasis.