ZNF263 promotes gastric cancer cell growth by regulating TXNDC9 transcription

Background: Zinc finger protein 263 (ZNF263) has been linked to the progression of several cancer types, although its significance in gastric cancer (GC) is poorly understood. This work sought to elucidate ZNF263’s biological function and underlying mechanism in GC formation. Methods: The expression of ZNF263 in GC tissues and its relationship with patient survival were investigated using public databases. ZNF263 protein expression was analyzed after transfecting GC cell lines with both the ZNF263 knockdown and overexpression plasmids. Cell viability and proliferation were assessed using Cell Counting Kit-8 (CCK8) and 5-Ethynyl-2′-deoxyuridine (EdU) assays, respectively. Flow cytometry was used to assess apoptosis rates, as well as the expression of associated proteins (cleaved-caspase3 and cleaved-Poly(ADP-ribose) polymerase) was analyzed by Western blot. Chromatin immunoprecipitation followed by quantitative Polymerase Chain Reaction (ChIP-qPCR) and Dual luciferase assay were used to validate the transcriptional regulation of Thioredoxin Domain Containing 9 (TXNDC9) by ZNF263. TXNDC9 mRNA levels were measured by quantitative Reverse Transcription (qRT)-PCR. Results: ZNF263 was highly elevated in GC tissues, and high expression was related with a poor patient prognosis. ZNF263 overexpression promoted the malignant development of GC cells, while ZNF263 knockdown suppressed cell growth and induced apoptosis. These effects were accompanied by increased levels of cleaved-caspase3 and cleaved-PARP. Mechanistically, ZNF263 directly bound to the TXNDC9 promoter region, enhanced TXNDC9 transcription, and increased TXNDC9 mRNA expression. ZNF263 also elevated luciferase activity driven by the wild type, but not mutant, TXNDC9 promoter. Conclusions: ZNF263 promotes GC cell growth and inhibits apoptosis, which may be related to ZNF263 promoting TXNDC9 transcription. ZNF263–TXNDC9 axis may serve as a potential therapeutic target in GC.

Apoptosis; Gastric cancer; Proliferation; TXNDC9; ZNF263

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