Oncogenic Function and Early Detection Potential of miRNA-10b in Oral Cancer as Identified by microRNA Profiling

Abstract

The miRNA participates in a variety of biologic processes, and dysregulation of miRNA is associated with malignant transformation. In this study, we determined specific profile of miRNA associated with oral cancer by using miRNA array screening method. There were 23 miRNAs found with considerably differential expressions between six oral cancer cell lines and five lines of normal oral keratinocytes, in which, 10 miRNAs showed the highest significant difference after independent examination by reverse transcription quantitative PCR. Eight molecules were upregulated, miR-10b, miR-196a, miR-196b, miR-582-5p, miR15b, miR-301, miR-148b, and miR-128a, and two molecules, miR-503 and miR-31, were downregulated. The most upregulated miR-10b was further examined, and its functions were characterized in two oral cancer cell lines. The miR-10b actively promotes cell migration (2.6-to 3.6-fold) and invasion (1.7-to 1.9-fold) but has minimal effect on cell growth or chemo-/radiosensitivity. Furthermore, miR-10b was considerably elevated in the plasma of xenografted tumor mice (20-fold). This upregulation of miR-10b in plasma was further shown in the patients with oral cancer [P < 0.0001, area under curve (AUC) ¼ 0.932] and precancer lesions (P < 0.0001, AUC ¼ 0.967), suggesting that miR-10b possesses a high potential to discriminate the normal subjects. In conclusion, we have identified at least 10 miRNAs significantly associated with oral cancer, including the most elevated miR-10b. The miR-10b actively participates in cancer formation by promoting cell migration and invasion. Our study using clinical samples suggests that plasma miR-10b has high potential as an early detection marker for oral cancer. Cancer Prev Res; 5(4); 665-74. Ó2012 AACR. Impact of this paper:1. miRNA signature of oral cancer was determined. 2. The oncogenic function of miR-10b in oral cancer was first demonstrated. 3. The potential of miR-10b as a circulating biomarker for the early detection of oral cancer was presented.

miRNAs as Essential Mediators of the Actions of Retinoic Acid in Neuroblastoma Cells

“…Consistent to that, it has been reported an association between lower miR-10a expression and lower overall survival for a subclass of neuroblastoma tumors (11q-tumor cohort) [29]. However other reports seem to involve the members of the miR-10 family as promoters of migration and metastasis in different tumors [33][34][35][36][37][38][39][40]. This apparent controversy may suggest that the role of the microRNAs from the miR-10 family in tumorigenesis and metastasis would depend on their molecular targets and therefore would depend on the cellular context.…”

A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes

“…MIR10B has been implicated in the past in multiple cancers, including in head and neck (58)(59)(60)(61)(62). Unlike in some cancers, its role in HNSCC is unclear (63).…”

The locus of microRNA-10b

“…miR-10b is upregulated in tumoral endothelial cells in response to tumorproduced growth factors, including VEGF, and administration of anti-miR-10b results in endothelial progenitor cells (EPC)-mediated impaired tumor growth in vivo. 32 miR-10b overexpression, besides breast cancer, associates with progression of oral and colorectal cancer, 33,34 pancreatic adenocarcinoma, 35,36 and glioblastoma. 31,37 In an orthotopic human glioma mouse model, inhibition of miRNA-10b diminishes the invasiveness, angiogenesis, and growth of the mesenchymal subtype-like glioma cells in the brain and significantly prolongs survival of glioma-bearing mice.…”