HMGA1 promotes the proliferation, migration, and invasion of uveal melanoma cells via the PI3K/Akt/MMP-9 pathway.

BACKGROUND

Uveal melanoma (UM) was prone to metastasis and had an extremely poor prognosis. High-mobility group protein A1 (HMGA1) was known to promote proliferation and invasion in various tumors, but its molecular mechanism in UM remained unclear.

OBJECTIVE

The effect of HMGA1 on the proliferation, migration, and invasion of UM cells was investigated, and whether it functioned through the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/matrix metalloproteinase-9 (MMP-9) pathway was explored.

METHODS

HMGA1 overexpression (OE) and knockdown (KD) models were established in two UM cell lines (C918, MUM-2B). Cell functions were assessed using MTT assay, EdU (5‑ethynyl‑2'‑deoxyuridine) incorporation assay, scratch wound healing assay, and Matrigel-Transwell assay. The expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), and MMP-9 was detected by Western blot (WB). Pathway intervention was performed using the PI3K inhibitor LY294002.

RESULTS

Compared with the control group, HMGA1 overexpression significantly up-regulated the proliferation, migration, and invasion abilities of both cell lines, and led to a fold-dependent up-regulation of PI3K/Akt pathway activation and MMP-9 expression. In contrast, HMGA1 knockdown significantly down-regulated the above indicators. After treatment with LY294002, the tumor-promoting effects induced by HMGA1 overexpression were significantly reversed.

CONCLUSION

HMGA1 significantly promoted the proliferation, migration, and invasion of UM cells from different origins (primary C918, metastatic MUM-2B) by activating the PI3K/Akt pathway and upregulating MMP-9 expression, suggesting its potential as a target for molecular targeted therapy in UM.