Journal
TRANSLATIONAL CANCER RESEARCH
Volume 12, Issue 2, Pages 310-+Publisher
AME PUBLISHING COMPANY
DOI: 10.21037/tcr-22-2045
Keywords
REG?; mantle cell lymphomas; NF-KB; apoptosis
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REG gamma regulates p-STAT3 expression and downregulates the NF-KB signaling pathway to promote MCL cell apoptosis by negatively regulating STAT3-mediated PSMB5 expression and subsequently upregulating IKB expression.
Background: Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL). REG gamma is important for tumor occurrence and development, but understanding of the specific role of REG gamma in MCL is lacking. We aimed to identify REG gamma effects on the proliferation and apoptosis of MCL cells and c larify the underlying mechanisms. Methods: JEKO-1 cells stably transfected with a doxycycline-inducible Tet-On system expressed high levels of REG gamma. JEKO-1 cells stably expressing shRNA-REG gamma to reduce REG gamma levels were constructed. Cell proliferation, apoptosis, and p-NF-KB, NF-KB, IkB, REG gamma, p-STAT3, STAT3, and PSMB5 levels in transfected cells and in transfected cells treated with Stattic, that is a nonpeptidic small molecule exhibited to selectively inhibit signal transducer and activator of transcription factor 3 through blocking the function of its SH2 domain, were analyzed using western blotting. Results: The proliferation of JEKO-1 cells was inhibited, and apoptosis was enhanced by increased expression of REG gamma (P<0.01). REG gamma inhibited MCL cell proliferation in a mouse tumor xenograft model by promoting apoptosis, increased the expression of the three IKB subunits and inhibited NF-KB signaling. Overexpressed REG gamma inhibited STAT3 and downregulated PSMB5 expression in MCL cells. Stattic downregulated PSMB5 and nuclear factor-kappa B (NF-KB) expressions and upregulated IKB epsilon expression in JEKO-1 cells. Conclusions: We found that REG gamma regulated p-STAT3 expression by accelerating its half-life and downregulated the NF-KB signaling pathway to promote MCL cell apoptosis by negatively regulating STAT3-mediated PSMB5 expression and subsequently upregulating IKB expression.
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