Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.
BACKGROUND
Oral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK.


RESULTS
Using miRNA microarrays, we profiled miRNA expression in OLK and malignantly transformed OLK (mtOLK) tissue samples. The upregulation of miR-31*, miR-142-5p, miR-33a, miR-1259, miR-146b-5p, miR-886-3p, miR-886-5p, miR-519d, and miR-301a along with the downregulation of miR-572, miR-611, miR-602, miR-675, miR-585, miR-623, miR-637, and miR-1184 in mtOLK were new observations. Fluorescence in situ hybridization (FISH) analyses confirmed that miR-31* is highly expressed in mtOLK. There was a significant difference between the FISH score (p<0.05) in patients with or without recurrent/newly formed OLK. Functional analyses demonstrated that a miR-31* inhibitor decreased apoptosis in the Leuk-1, which is an immortalized oral epithelial cell line spontaneously derived from an oral leukoplakia lesion. miR-31* regulated apoptosis, cell proliferation, migration, and invasion in the HOIEC, which is a HPV E6/E7-immortalized oral epithelial cell line. Furthermore, miR-31* modulated the biological functions of apoptosis, cell proliferation, cell cycle, migration, and invasion in the oral squamous cell carcinoma cell line, Cal-27. Using bioinformatic analyses and dual luciferase reporter assays, we determined that the 3' untranslated region of fibroblast growth factor 3 (FGF3) is the target of miR-31*. Expression of FGF3 was downregulated or upregulated in the presence of a miR-31* mimic or inhibitor, respectively.


CONCLUSIONS
Upregulation of miR-31* is negatively associated with recurrent/newly formed OLK. MiR-31* may exert similar but distinguishable effects on biological function in oral cells with different malignant potential. FGF3 is the target of miR-31*. miR-31* may play an important role during OLK progression through regulating FGF3. MiRNA* strands may also have prominent roles in oral carcinogenesis.
Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Wen
W
Xiao
Zhe-Xuan
ZX
Bao
Chen-Yang
CY
Zhang
Xiao-Yun
XY
Zhang
Lin-Jun
LJ
Shi
Zeng-Tong
ZT
Zhou
Wei-Wen
WW
Jiang
D017209:Apoptosis / Q000235:genetics; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D051518:Fibroblast Growth Factor 3 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence; D015854:Up-Regulation
C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; C534612:MIRN31 microRNA, human; D035683:MicroRNAs