HMGA1 exacerbates tumor progression by activating miR-222 through PI3K/Akt/MMP-9 signaling pathway in uveal melanoma.

High-mobility group A1 (HMGA1), an architectural transcription factor, participates in different human tumors' biological progression. HMGA1 overexpression is associated with malignant cellular behavior in a wide range of cancers but the underlying mechanism remains poorly illuminated. In this study, we showed PI3K/Akt/MMP9 pathway activity could be positively regulated by HMGA1 using western blotting, real-time polymerase chain reaction (RT-PCR) and immunochemistry both in vitro (C918 and MUM-2B cell lines) and in vivo (xenograft mouse model). Later, MiRTarBase was used to identify the relationship between HMGA1 and miR-222-3p, we found miR-222 is positively regulated by HMGA1. Moreover, the proliferation and migration of UM cells significantly increased in the miR-222 mimics group and decreased in the miR-222 inhibitor group detected by the Annexin V-FITC apoptosis detection kit, CCK-8 and scratch wound-healing. The p-PI3K, p-Akt and MMP9 expressions were elevated in UM cells transfected with miR-222 mimics, and suppressed in the miR-222 inhibitor group. Together, our study highlights that HMGA1 acts as a pivotal regulator in UM tumor growth, proposing a critical viewpoint that HMGA1 expedites progression through the PI3K/Akt/MMP9 pathway and oncogenic miR-222 in UM.