Aberrant expression of the sFRP and WIF1 genes in invasive non-functioning pituitary adenomas.
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (p = 0.002, p < 0.001). Univariate analysis showed a significant correlation between tumor invasion and low expression of WIF1 and sFRP4 (p = 0.002, p < 0.001). A similar trend was observed when analyzing the mRNA and protein levels through RT-PCR and western blot experiments. Methylation of the WIF1 promoter was significantly increased in invasive NFPAs compared with the noninvasive group (p = 0.004). The average progression free survival time in the high WIF1 group was longer than that in the low WIF1 group (p = 0.025). Furthermore, RT-PCR measured the levels of 11 miRNAs targeting WIF1 according to the Targetscan database and PubMed. The levels of miRNA-137, miRNA-374a-5p and miRNA-374b-5p in the invasive group were 0.037-fold, 0.577-fold and 0.44-fold that of the noninvasive group (p = 0.003, p = 0.049 and p = 0.047). Overexpression of miRNA-137 could inhibit the proliferation and invasion of GH3 cells through cell viability and Transwell experiments (p < 0.05). Furthermore, the WIF1 level was upregulated after overexpression of miRNA-137 compared with miRNA-137-NC (control miRNA) in GH3 cells. Our data suggest that WIF1 may be potential biomarker for the aggressiveness of NFPAs. miRNA-137 plays an important role in the Wnt signaling pathway by affecting promoter methylation of WIF1.
['Song|Wang|W|', 'Qian|Liu|L|', 'Jing|Guo|G|', 'Jie|Feng|F|', 'Xiaosong|Shan|S|', 'Chunhui|Liu|L|', 'Yangfang|Li|L|', 'Guilin|Li|L|', 'Gao|Hua|H|', 'Yazhuo|Zhang|Z|']
D048868:Adaptor Proteins, Signal Transducing D000236:Adenoma D000328:Adult D000368:Aged D045744:Cell Line, Tumor D049109:Cell Proliferation D019175:DNA Methylation D005260:Female D015972:Gene Expression Regulation, Neoplastic D052138:Genes, Neoplasm D006801:Humans D008297:Male D035683:MicroRNAs D008875:Middle Aged D009361:Neoplasm Invasiveness D010911:Pituitary Neoplasms D000077982:Progression-Free Survival D011401:Promoter Regions, Genetic D011518:Proto-Oncogene Proteins D012097:Repressor Proteins D015854:Up-Regulation D055815:Young Adult
WIF1 Invasive Non-functioning pituitary adenomas miRNA-137 sFRP genes