ABSTRACT
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.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/pathology , Gene Expression Regulation, Neoplastic , Interleukins/metabolism , MicroRNAs/genetics , Mouth Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Movement , Cell Proliferation , Humans , Interleukins/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Neoplasm Invasiveness , Proto-Oncogene Proteins c-akt/genetics , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
Cell Movement , Hyaluronan Receptors/metabolism , MicroRNAs/metabolism , Mouth Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , rho-Associated Kinases/metabolism , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Lab-On-A-Chip Devices , MicroRNAs/genetics , Microfluidic Analytical Techniques/instrumentation , Mouth Neoplasms/enzymology , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Neoplasm Invasiveness , Signal Transduction , Squamous Cell Carcinoma of Head and Neck/enzymology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Time FactorsABSTRACT
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.
