Up‐regulation of miR‐455‐5p by the TGF‐β–SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B

Abstract

MicroRNAs (miRNAs) are involved in the tumourigenesis of various cancers by regulating their downstream targets. To identify the changes of miRNAs in oral squamous cell carcinoma (OSCC), we investigated the expression profiles of miRNAs in 40 pairs of OSCC specimens and their matched non-tumour epithelial tissues. Our data revealed higher miR-455-5p expression in the tumour tissues than in the normal tissues; the expression was also higher in oral cancer cell lines than in normal keratinocyte cell lines. MiR-455-5p knockdown reduced both the anchorage-independent growth and the proliferative ability of oral cancer cells, and these factors increased in miR-455-5p-overexpressing cells. Furthermore, by analysing the array data of patients with cancer and cell lines, we identified ubiquitin-conjugating enzyme E2B (UBE2B) as a target of miR-455-5p, and further validated this using 3'-untranslated region luciferase reporter assays and western blot analysis. We also demonstrated that UBE2B suppression rescued the impaired growth ability of miR-455-5p-knockdown cells. Furthermore, we observed that miR-455-5p expression was regulated, at least in part, by the transforming growth factor-β (TGF-β) pathway through the binding of SMAD3 to specific promoter regions. Notably, miR-455-5p expression was associated with the nodal status, stage, and overall survival in our patients, suggesting that miR-455-5p is a potential marker for predicting the prognosis of patients with oral cancer. In conclusion, we reveal that miR-455-5p expression is regulated by the TGF-β-dependent pathway, which subsequently leads to UBE2B down-regulation and contributes to oral cancer tumourigenesis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Exploring specific prognostic biomarkers in triple-negative breast cancer

“…To the best of our knowledge, only one study indicated that miR-455-5p was differentially expressed between invasive and non-invasive breast cancer based on the analyses of archived FFPE tissues and laboratory-based barcoded cDNA library 46 . In other cancers, miR-455-5p has been reported as a potential oncogene for non-small cell lung cancer 47 , colon cancer 48 and oral squamous cancer 49 . In our present study, we confirmed these 4 screened DEmiRNAs not only differentially expressed in TNBC cell lines compared to normal breast cell line, but also showed effective regulation on cell proliferation and migration.…”

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

“…MiRNA-455 (miR-455) is recognized as a broadly conserved noncoding RNA that has been implicated in various cancers. The function of miR-455 has been confirmed in prostate cancer [51], gastric cancer [52], and oral squamous cancer cells [53]. However, the potential effect of miR-455-3p has rarely been explored in PDAC.…”

Identification of exosomal miR-455-5p and miR-1255a as therapeutic targets for breast cancer

“…Functional assays showed that miR-455-3p enhanced cell proliferative, invasive and migratory abilities in TNBC cell lines [28]. Furthermore, studies on non-small cell lung cancer [29], colon cancer [30] and oral squamous cancer cells [31] also verified that miR-455-5p may function as a potential oncogene. In addition, our study also showed exosomal miR-455-5p in breast cancer cells may influence the phenotype of neighboring or distant non-malignant recipient cells by decreasing the expression of CDKN1B gene.…”