Endocrine Abstracts

Objective: To analyze the role of miRNAs previously found to be differentially expressed in patients with ACTH-dependent Cushing syndrome (CS).

Materials and methods: We analyzed putative targets of three microRNAs, which were previously found to be differentially expressed in ACTH-dependent CS patients: miR-16-5p, miR-145-5p, miR-7g-5p. We used TargetScan (TS) and DIANA tools (DT) predictions.

Results: We found different plasma expression of miR-16-5p, miR7g-5p and miR-145-5p in CD (n=28) compared to ACTH-ectopic syndrome (n=13). MiR- 16-5p was differently expressed in plasma samples from healthy subjects (n=11) compared to both CD and ACTH-ectopic CS. MiR- 145-5p expression differed between ACTH-ectopic CS vs healthy subjects, but not CD vs healthy subjects; whereas miR- 7g-5p was differently expressed in CD vs healthy control, but did not differ from ACTH-ectopic CS vs healthy subjects. Using TargetScan (TS) and DIANA tools (DT) we evaluated HMGA1 and HMGA2 as possible targets of miR-16-5p and mir-7g-5p, which may explain the rare incidence of malignancy in CD and non-invasive pituitary tumor growth. miR-16-5p also targets oncogene SOX5 that is known to stimulate the progression of various cancers. By targeting Sox5 miR-16-5p inhibit pituitary tumor cell proliferation, invasion and migration. Another mir-16-5p target gene is BCL2 that regulates apoptosis. miR-145-5p inhibits the mTOR signaling pathway by targeting AKT3 and can regulate cell proliferation, invasion and apoptosis.

Conclusions: Our findings demonstrate that miR-16-5p, miR-145-5p, miR-7g-5p can be involved in development of ACTH-dependent Cushing syndrome which might be helpful to evaluate malignant potential or therapeutic efficiency in ACTH-dependent Cushing syndrome.