# Role of B1 antisense RNA on the proliferation and killing tumor ability of aged mouse spleen lymphocytes

## TL;DR

This study shows that B1 antisense RNA can boost the immune function of aged mouse lymphocytes by improving their proliferation and tumor-killing ability.

## Contribution

The novel finding is that B1 antisense RNA enhances immune function in aged lymphocytes through regulation of senescence-related genes and ZFP92 protein activity.

## Key findings

- B1 asRNA increased lymphocyte proliferation and S phase cell numbers in aged mice.
- B1 asRNA reduced apoptosis and modulated senescence-related and transcription factor genes.
- B1 asRNA improved tumor cell killing and increased ZFP92 binding to key gene promoters.

## Abstract

To explore whether mouse short interspersed nuclear element B1 antisense RNA (B1 antisense RNA, B1 asRNA) could improve the proliferation activity and killing tumor function of spleen lymphocytes from aged mice and to investigate the underlying mechanisms, we transfected B1 asRNA into spleen lymphocytes isolated from 12-month-old mice. We found that B1 asRNA substantially increased the proliferative rate of lymphocytes, the number of EdU-positive cells and the number of S phase cells. B1 asRNA decreased the apoptosis of lymphocytes and regulated the mRNA expression levels of senescence-related genes and transcription factor genes. B1 asRNA enhanced the ability of killing S180 and H22 tumor cells of lymphocytes. The immunofluorescence results showed that B1 asRNA increased the fluorescence intensity of ZFP92 protein in the nuclei, and the ChIP-qPCR results indicated that B1 asRNA promoted the binding of ZFP92 protein to DNA sequences of Nanog, Oct4, Sox2, Klf4 and Myc genes. We believe that B1 asRNA regulates the expression of senescence-related genes, cell cycle genes and transcription factor genes and that ZFP92 protein may play an important role in the process of B1 asRNA regulating gene expression. These studies suggest that B1 asRNA can enhance immune functions of senescent lymphocytes.

The online version contains supplementary material available at 10.1038/s41598-025-23139-z.