Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma

Abstract

Objectives MicroRNA deregulation is a critical event in head and neck squamous cell carcinoma (HNSCC). Several microRNA profiling studies aimed at deciphering the microRNA signatures of HNSCC have been reported, but there tends to be poor agreement among studies. The objective of this study was to survey the published microRNA profiling studies on HNSCC, and to assess the commonly deregulated microRNAs in an independent sample set. Materials and Methods Meta-analysis of 13 published microRNA profiling studies was performed to define microRNA signatures in HNSCC. Selected microRNAs (including members of miR-99 family) were evaluated in an independent set of HNSCC cases. The potential contributions of miR-99 family to the tumorigenesis of HNSCC were assessed by in vitro assays. Results We identified 67 commonly deregulated microRNAs. The up-regulation of miR-21, miR-155, miR-130b, miR-223 and miR-31, and the down-regulation of miR-100, miR-99a and miR-375 were further validated in an independent set of HNSCC cases with quantitative RT-PCR. Among these validated microRNAs, miR-100 and miR-99a belong to the miR-99 family. Our in vitro study demonstrated that restoration of miR-100 to the HNSCC cell lines suppressed cell proliferation and migration, and enhanced apoptosis. Furthermore, ectopic transfection of miR-99 family members down-regulated the expression of insulin-like growth factor 1 receptor (IGF1R) and mechanistic target of rapamycin (mTOR) genes. Conclusion In summary, we described a panel of frequently deregulated microRNAs in HNSCC, including members of miR-99 family. The deregulation of miR-99 family contributes to the tumorigenesis of HNSCC, in part by targeting IGF1R and mTOR signaling pathways.

Circulating microRNAs as novel prognosis biomarkers for head and neck squamous cell carcinoma

“…16,17 Tumor suppressor miRNAs are often downregulated in cancer cells. Enhanced expression of miR-99a could lead to a reduction in cell proliferation, cell migration and increased apoptosis, while the down-regulated expression of miR-99a attenuates the inhibitory effect of cell migration and invasion in HNSCC cell lines.…”

Mechanisms of Invasion in Head and Neck Cancer

“…188 MiR-375 targets metadherin (MTDH) [189][190][191][192][193] and miR-504 targets forkhead box P1 (FOXP1), 194 also important for invasion. Finally, there is a small group of targets whose direct function in invasion are unclear, such as programmed cell death 4 (PDCD4), 195 targeted by miR-21, BCL2 binding component 3 (BBC3), 196 and mitochondrial superoxide dismutase 2 (SOD2), 197 targeted by miR-222.…”

Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study

“…Additionally, hsa-miR-143 and hsa-miR-34a are direct transcriptional targets of p53 (Chang et al, 2007;RaverShapira et al, 2007;Zhang et al, 2013a). The other candidate, hsa-miR-99a, known for its involvement in the regulation of AKT/mTOR signaling pathway (Chen et al, 2012), is independent of the p53 pathway. However, a connection between the p53 and AKT/mTOR signaling pathway has been previously established (Feng et al, 2005;Levine et al, 2006).…”