ZNF32 promotes the self-renewal of colorectal cancer cells by regulating the LEPR-STAT3 signaling pathway

Abstract

AbstractDue to the self-renewal characteristics and tumorigenic abilities of cancer stem cells (CSCs), CSCs have been demonstrated to play vital roles in carcinogenesis and antitumor therapy. Our previous report found that Krüppel-like family members (KLFs) and zinc finger protein 32 (ZNF32) play oncogenic roles in carcinogenesis. However, the roles and mechanism of ZNF32 in CSCs are still unknown. Our study demonstrated that ZNF32 was highly expressed in colorectal CSCs, which promoted their self-renewal capacity and tumorigenicity. Overexpression of ZNF32 in colorectal cancer (CRC) cells increased their self-renewal capacity. Furthermore, we identified the leptin receptor (LEPR) as the downstream target gene of ZNF32 and verified that the ZNF32-mediated regulation of CRC self-renewal is achieved via the LEPR- signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ZNF32 regulated the expression of SOX2, a core transcription factor in stem cells. Finally, we demonstrated that ZNF32 and LEPR were positively correlated in CRC tissues. ZNF32 expression was negatively correlated with the prognosis of CRC patients. Therefore, therapeutically targeting the ZNF32-LEPR-STAT3 pathway in the clinic is tempting.