Upregulation of miR-31*Is Negatively Associated with Recurrent/Newly Formed Oral Leukoplakia

作者：Xiao, Wen^*; Bao, Zhe-Xuan; Zhang, Chen-Yang; Zhang, Xiao-Yun; Shi, Lin-Jun; Zhou, Zeng-Tong; Jiang, Wei-Wen

来源：PLos One, 2012, 7(6): e38648.

DOI：10.1371/journal.pone.0038648

• SQUAMOUS-CELL CARCINOMA
• IN-SITU HYBRIDIZATION
• HEPATOCELLULAR-CARCINOMA
• NASOPHARYNGEAL CARCINOMA
• 11Q13 AMPLIFICATION
• GENE AMPLIFICATION
• EPITHELIAL-CELLS
• THYROID-CANCER
• MICRORNA
• EXPRESSION

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. @@@ Methodology/Principal Findings: 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/Significance: 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.

• 出版日期2012-6-18
• 单位上海交通大学