Tissue Eng Regen Med.  2023 Dec;20(7):1145-1159. 10.1007/s13770-023-00585-2.

circ_SPEF2 Regulates the Balance of Treg Cells by Regulating miR-16-5p/BACH2 in Lymphoma and Participates in the Immune Response

• Zhou J
• Xu M
• Chen Z
• Huang L
• Wu Z
• Huang Z
• Liu L

• KMID: 2548534
• DOI: http://doi.org/10.1007/s13770-023-00585-2

Abstract

BACKGROUND
This study aims to explore the potential mechanism of action of the newly discovered hsa_-circ_0128899 (circSPEF2) in diffuse large B-cell lymphoma (DLBCL).
METHODS
circSPEF2, miR-16-5p and BTB and CNC homologue 2 (BACH2) expression patterns in DLBCL patients and cell lines were studied by RT-qPCR. The biological function of circSPEF2 in vitro and in vivo was investigated by function acquisition experiments. The proliferation activity of lymphoma cells was detected by MTT. Bax, Caspase-3, and Bcl-2 were determined by Western Blot. Apoptosis and the ratio of CD4 to Treg of immune cells in the co-culture system were analyzed by flow cytometry. The mechanism of action of circSPEF2 in DLBCL progression was further investigated by RIP and dual luciferase reporter experiments.
RESULTS
circSPEF2 was a circRNA with abnormally down-regulated expression in DLBCL. Increasing circSPEF2 expression inhibited the proliferative activity and induced apoptosis of lymphoma cells in vitro and in vivo, as well as increased CD4⁺ T cells and decreased Treg cell proportion of immune cells in the tumor microenvironment. Mechanically, circSPEF2 was bound to miR-16-5p expression, while BACH2 was targeted by miR-16-5p. circSPEF2 overexpressionmediated effects on lymphoma progression were reversible by upregulating miR-16-5p or downregulating BACH2.
CONCLUSIONS
circSPEF2 can influence DLBCL progression by managing cellular proliferation and apoptosis and the proportion of immune cells Treg and CD4 through the miR-16-5p/BACH2 axis.

Keyword

circSPEF2; miR-16-5p; BACH2; Lymphoma