
-   MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia [PMID: 31980446].
-   The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing [PMID: 34272366].

## Summary

Slfn4 functions as a negative regulator of cell population proliferation in the intestine [CS: 9]. When downregulated, as seen in the colonic mucosa of aged rats or during exposure to certain intestinal toxins, its absence leads to dysregulated cellular proliferation [CS: 8]. This dysregulation is likely due to the loss of Slfn4's inhibitory influence on cell growth pathways [CS: 7]. Typically, Slfn4 maintains homeostasis by ensuring a controlled rate of cellular turnover [CS: 8], but its reduction disrupts this balance, potentially leading to excessive cell proliferation and contributing to pathologies like hyperplasia or cancer [CS: 6].

The upregulation of Slfn4 in response to cyclic strain in rat small intestine epithelial cells signifies its role in intestinal epithelial differentiation [CS: 7]. This upregulation likely functions as a protective response to stress, where Slfn4 promotes the maturation and specialization of epithelial cells [CS: 6]. Enhanced epithelial differentiation, facilitated by Slfn4, helps maintain the integrity of the intestinal barrier and optimizes absorptive functions [CS: 8], counteracting the disruptive effects of intestinal stressors and toxins [CS: 7].
