# miR-3921 functions as a tumor suppressor and negatively regulates RIPK1 in gastric cancer

## TL;DR

This study shows that miR-3921 acts as a tumor suppressor in gastric cancer by targeting RIPK1, suggesting both could be potential treatment targets.

## Contribution

The novel finding is that miR-3921 directly targets and downregulates RIPK1 in gastric cancer cells.

## Key findings

- miR-3921 mimics reduced cell proliferation and migration while increasing apoptosis in gastric cancer cells.
- miR-3921 binds to and downregulates RIPK1 expression by targeting its 3′-UTR region.
- RIPK1 expression is higher in gastric cancer tissues compared to normal tissues.

## Abstract

MicroRNAs (miRNAs) are critical regulators of biological processes associated with gastric cancer (GC) progression. Although previous studies have suggested a role for miR-3921 in GC, its function remains unclear. This study investigates the effect of miR-3921 on cell proliferation, migration, and apoptosis in GC, and explores its potential downstream targets.

The gastric cancer (GC) cell lines, MKN-45 and AGS, were transfected using miR-3921 mimics and inhibitors and the expression of miR-3921 was confirmed by qRT-PCR. The effects of miR-3921 on MKN-45 and AGS cell proliferation, apoptosis and migration were assessed using the CCK-8 assay, flow cytometry, and transwell and wound healing assays, respectively. Bioinformatic analyses based on data from Luciferase reporter assays tested the interaction between miR-3921 and receptor-interacting protein kinase 1 (RIPK1). Western blotting was used to evaluate the regulatory effect of miR-3921 on RIPK1 expression. The Cancer Genome Atlas (TCGA) was employed to assess the expression levels of receptor-interacting protein kinase 1 (RIPK1) in GC versus normal tissues. Survival data were analyzed using datasets obtained from TCGA and the Gene Expression Omnibus.

miR-3921 mimics suppressed proliferation and migration while promoting apoptosis in MKN-45 and AGS cells. The opposite effects were observed using a miR-3921 inhibitor. miR-3921 directly targeted RIPK1 by binding to its 3′-untranslated region (UTR) which downregulated its expression. Furthermore, we observed elevated RIPK1 expression levels in GC tissues compared to normal tissues. Survival analysis indicated varying prognostic significance of RIPK1 across multiple datasets.

miR-3921 inhibits the progression of GC, and can bind to and regulate RIPK1, indicating that both miR-3921 and RIPK1 may represent potential therapeutic targets in GC.