osu-03012 and Retinoblastoma

There is extensive evidence suggesting that microRNAs (miRs) can modulate the activity of oncogenes and tumor suppressors, and are associated with the occurrence of cancer. In the present study, the function of miR‑363‑3p in the progression of retinoblastoma (RB) was investigated. miR‑363‑3p expression in RB was decreased, and miR‑363‑3p protein levels were found to be inversely correlated with phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α (PIK3CA) levels. Overexpression of miR‑363‑3p in an in vitro model of RB revealed that miR‑363‑3p had anticancer effects on RB and regulated PIK3CA, pyruvate dehydrogenase kinase 1 (PDK1) and phosphorylated protein kinase B (p‑AKT) protein expression. Downregulation of miR‑363‑3p promoted cell proliferation of RB cells through PIK3CA, PDK1 and p‑AKT protein expression. Knockdown of PIK3CA increased the anticancer effects of miR‑363‑3p in RB cells. Treatment with OSU‑03012, a PDK1 inhibitor, accelerated the anticancer effects of miR‑363‑3p in RB cells. Taken together, the results demonstrate that miR‑363‑3p functions as a tumor suppressor in RB by targeting PIK3CA.

Topics: Cell Line, Tumor; Cell Proliferation; Cell Survival; Class I Phosphatidylinositol 3-Kinases; Disease Progression; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Middle Aged; Proto-Oncogene Proteins c-akt; Pyrazoles; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Retinoblastoma; Signal Transduction; Sulfonamides