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

Due 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.

Hsa­circRNA­G004213 promotes cisplatin sensitivity by regulating miR­513b­5p/PRPF39 in liver cancer.

In recent years, increasing evidence has confirmed that exosomal circular RNAs (circRNAs) serve a crucial role in the prognostic prediction and diagnosis of liver cancer (LC). The present study compared the expression patterns of exosomal circRNAs during transarterial chemoembolization (TACE). CircRNA sequencing analysis identified 390 differentially expressed circRNAs between the prior TACE and following the first TACE operation groups and 489 differentially expressed circRNAs between the prior to TACE and following the second TACE operation groups. Gene Ontology analysis of the differentially expressed circRNAs demonstrated that they were associated with fatty acid metabolism, receptor binding and membrane protein complexes. Kyoto Encyclopedia of Genes and Genomes pathway analysis predicted that protein digestion and absorption pathways were activated following TACE. A novel gene was screened out; hsa­circRNA­G004213 (circ­G004213) was significantly upregulated following TACE (fold change >10, P < 0.01). Further analysis found circ­G004213 significantly increased the cisplatin sensitivity of HepG2 cells and positively associated with the prognosis of tumor­bearing mice. Based on the potential downstream miRNAs and mRNAs, the circRNA­miRNA­mRNA network was constructed. It was demonstrated that circ­G004213 regulated cisplatin resistance via the miR­513b­5p/PRPF39 axis. Finally, the present study confirmed that circ­G004213 was positively associated with the prognosis of patients with LC following TACE. Therefore, circ­G004213 may be used as an indicator for predicting the efficacy of TACE.