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Diagnostic potential of miR-483 family for IGF-II producing non-islet cell tumor hypoglycemia.

OBJECTIVE
In insulin-like growth factor II (IGF-II) producing non-islet cell tumor hypoglycemia (NICTH), high molecular weight forms of IGF-II (big IGF-II) are produced as a cause of spontaneous hypoglycemia. MicroRNA (miRNA)-483 family, encoded in an intron lesion of IGF2 gene, is suggested to be co-expressed with IGF-II. Here, we tested whether serum miR-483-5p and -3p levels are associated with the presence of big IGF-II in NICTH.


DESIGN
Serum samples from patients who were suspected to have IGF-II producing NICTH (n=42) were tested. MiR-483-5p and -3p levels were evaluated using quantitative PCR. IGF-II level was analyzed using ELISA. The presence of big IGF-II was identified by Western blotting.


RESULTS
Big IGF-II was detected in the sera of 32 patients. MiR-483-5p (P=0.0015) and -3p (P=0.027) levels were significantly higher in sera with big IGF-II (n=32) than in those without (n=10), whereas serum IGF-II level (P=0.055) was not significantly different between the groups. The median serum concentration of miR-483-5p was ~10 times higher than that of miR-483-3p. Although a strong correlation was observed between the two miRNAs (r=0.844, P<0.0001), but neither of which was correlated with serum IGF-II level. The areas under the receiver operating characteristic curves of miR-483-5p (0.853) and -3p (0.722) were higher than that of IGF-II (0.694) for detecting the presence of big IGF-II.


CONCLUSION
The associations of serum miR-483-5p and -3p levels with the presence of big IGF-II suggest the diagnostic potential of these miRNAs for IGF-II producing NICTH.