GSE107445
Deep sequencing reveals the regulatory network of microRNA-transcription factor in paired normal and OSCC tissue suggesting a tumor suppress role of circadian clock gene RORa
The molecular interplay between miRNA and mRNA is critical for tumorigenesis, whereas it is not comprehensively profiled in OSCC. Here, we aimed to explore the potential network of miRNAs-mediated genes. Furthermore, the cooperative effect of miRNAs on RORa in tumor proliferation was elucidated. Four pairs of cancer and adjacent normal tissues were collected for high-throughput sequencing. The regulatory interactions between differentially expressed miRNAs and mRNAs were performed by bioinformatics analysis. Luciferase reporter assay and qRT-PCR assay were used to examine the effects of miRNAs on RORa. The CCK8 assay and mice xenografts assay were used to assess the role of RORa on OSCC proliferation in vitro and in vivo. Western blotting was used to detect the total and phosphorylated p53 protein level in cells with enforced or suppressed RORa expression.Differentially expressed mRNAs and miRNAs between paired OSCC and normal tissues were identified. The negative correlation networks between the up-regulated miRNA and down-regulated transcription factors (TFs) were determined. Five miRNAs (miR-503-5p, miR-450b-5p, miR-27a-3p, miR-181a-5p, miR-183-5p) were testified to directly target RORa, and resulted in a more stronger effect on RORa suppression by mixing together. In addition, RORa was detected to be generally decreased in 44 OSCC samples and significantly suppressed the proliferation of OSCC cells in vitro and in vivo. Attenuated RORa decreased p53 protein expression and suppressed p53 phosphorylation activity. The study revealed the possible miRNAs-mediated TFs network in OSCC and identified the cooperative miRNAs effect on RORa expression in OSCC proliferation. Overall design: four pairs of cancer and adjacent normal epithelia specimens