TY - JOUR
T1 - Diagnostic potential of miR-483 family for IGF-II producing non-islet cell tumor hypoglycemia
AU - Nagao, Mototsugu
AU - Fukuda, Izumi
AU - Asai, Akira
AU - Esguerra, Jonathan L.S.
AU - Hizuka, Naomi
AU - Eliasson, Lena
AU - Sugihara, Hitoshi
N1 - Funding Information:
This work was supported by European Foundation for the Study of Diabetes and Japan Diabetes Society (M N?, Scandinavia-Japan Sasakawa Foundation (M N?, Sumitomo Life Welfare Foundation (M N?, Swedish Research Council (2019-01406; L E?, Diabetes Research and Wellness
Funding Information:
This work was supported by European Foundation for the Study of Diabetes and Japan Diabetes Society (M N), Scandinavia-Japan Sasakawa Foundation (M N), Sumitomo Life Welfare Foundation (M N), Swedish Research Council (2019-01406; L E), Diabetes Research and Wellness Foundation (L E)
Publisher Copyright:
© 2021 European Society of Endocrinology Printed in Great Britain
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
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U2 - 10.1530/EJE-20-0706
DO - 10.1530/EJE-20-0706
M3 - Article
C2 - 33112286
AN - SCOPUS:85096080247
VL - 184
SP - 41
EP - 49
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 1
ER -