ADAM32 Oncogene in Hepatoblastoma Is Regulated by IGF2BP2

Background/Objectives: The membrane protein a disintegrin and metalloproteases (ADAMs) are highly expressed in various human carcinomas and play an important role in cancer characteristics. And among these, ADAM32 is highly expressed in hepatoblastoma (HBL) and plays an important role in oncogenic properties. However, the regulatory mechanism has not been determined. Recently, it has been reported that some ADAMs are regulated by HIF, which is an important transcription factor in response to hypoxia. Therefore, we decided to study the regulatory mechanisms of ADAM32 under hypoxic conditions by using HBL, breast, and lung cancer cell lines. Methods/Results: When these cells were exposed to 1% O₂ (hypoxia), it was found that the levels of ADAM32 increased at 48 h in HepG2, MCF7, and MDA-MB-231 but not in HUH-6 or lung cancer lines. However, the promoter activity of the ADAM32 gene in HepG2 remained unchanged under hypoxic conditions, suggesting that the level of ADAM32 in HBL is regulated by factors other than the promoter activity. From the microarray data, we found that the level of IGF2BP2, which is an m⁶A-related molecule, correlated with that of ADAM32, and these levels were decreased by HIF1A knockdown. And IGF2BP2 knockdown decreased the expression of ADAM32 and attenuated the increased expression of ADAM32 under hypoxic conditions. Conclusions: This study demonstrated that the oncogenic gene ADAM32 is regulated by IGF2BP2 and that IGF2BP2 could be a molecular target for HBL anticancer therapy.