ThPOK transcriptionally inactivates TNFRSF12A to increase the proliferation of T cells with the involvement of the NF-kB pathway.

Abstract

Gastric cancer (GC), originated from gastric mucosa, is a malignant tumor causing numerous deaths globally. The present study used the coculture of T cells with supernatant of the GC cells (HGC-27, SNU-1) and investigated the function and regulatory mechanism of Zinc finger and BTB domain containing 7B (ZBTB7B, alias ThPOK) on T cell proliferation. Flow cytometry analysis was used to measure the proliferation of CD3+ T cells and IFN-γ+ T cells. We found that low level of ThPOK was associated with poor prognosis in GC patients. ThPOK was lowly expressed in GC cells at the mRNA and protein levels. ThPOK overexpression inhibited GC cell viability and promoted proliferation of T cells. ThPOK was identified to function as a transcription factor for TNFRSF12A. TNFRSF12A was upregulated in GC tissues and cells and high level of TNFRSF12A was associated with poor prognosis in GC patients. ThPOK knockdown elevated TNFRSF12A level in GC cells. ThPOK was revealed to bind with the promoter of TNFRSF12A. TNFRSF12A silencing also inhibited GC cell viability and promoted T cell activation and proliferation. Additionally, ThPOK was demonstrated to inactivate the NF-kB pathway by downregulating TNFRSF12A in GC cells. Overall, ThPOK suppresses cell viability in GC and increases the activation and proliferation of T cells by targeting TNFRSF12A to inactivate the NF-kB pathway.