Elevated levels of serum MiR-152 and miR-24 in uterine sarcoma: potential for inducing autophagy via SIRT1 and deacetylated LC3.

BACKGROUND: MiRNAs may be associated with the risk of uterine sarcoma and related molecular mechanism remains unclear.

METHODS: A total of 101 patients with uterine sarcoma (cases) and 54 healthy subjects (controls) were enrolled. The levels of serum miR-152, miR-205, miR-222, miR-24, miR-150 and sirtuin 1 (SIRT1, an NAD +-dependent class III histone deacetylase) were measured by qRT-PCR. HeLa cells were transfected with the mimics of miR-152 and miR-24. The autophagic rates, and the levels of SIRT1 and acetylation of microtubule-associated protein 1A/1B-light chain 3 (LC3) were measured.

RESULTS: Levels of miR-152, miR-24 and SIRT1 decreased while the levels of miR-205, miR-222 and miR-150 increased in cases vs. controls (all P < 0.05). All miRNAs were linked with stage of the cases' sarcoma (all P = 0.001). Kaplan-Meier analysis demonstrated uterine sarcoma patients have better survival rates with high-level miR-152 and miR-24, with a five-year overall survival of 21.8% and 67.5%, respectively (P  =  0.003 and 0.004). The mimics of miR-152 and miR-24 induced autophagy by increasing the level of SIRT1, which deacetylated LC3.

CONCLUSION: Present findings demonstrate altered miRNA species in uterine sarcoma that are linked to disease stage, and a new molecular mechanism, by which miR-152 and miR-24 promote autophagy by activating SIRT1 and deacetylating LC3.