Fig 2: FLRT2 could counteract the effects of miR-7-5p inhibition on IL-1β-treated chondrocytes. A FLRT2 expression was promoted in chondrocytes transfected with miR-7-5p inhibitor and restored in chondrocytes co-transfected with miR-7-5p inhibitor and si-FLRT2. *P < 0.05, **P < 0.01; ns, not significant. B–D The suppression of FLRT2 could neutralize the effects of miR-7-5p inhibition on the viability (B) and apoptosis (C–D) of IL-1β-treated chondrocytes. **P < 0.01; ns, not significant. E Relative expression levels of FLRT2, MMP13, ADAMTS5, Collagen II, and Aggrecan after transfection were detected by western blot analysis. **P < 0.05; ns, not significant

Fig 3: FLRT2 was a target of miR-7-5p. A Three mRNAs including SSX2IP, FLRT2, and NREP were screened out by performing interaction analysis. B Dual-luciferase reported assay was applied to verify the targeting relationship between miR-7-5p and FLRT2. **P < 0.01, compared with the miR-NC group. C–D FLRT2 mRNA C and protein D expressions were significantly decreased in IL-1β-treated chondrocytes. **P < 0.01, compared with the control group. E–F FLRT2 mRNA and protein expressions were significantly decreased following the transfection with miR-7-5p mimics. **P < 0.01, compared with the miR-NC group

Fig 4: FLRT2 silences suppresses ferroptosis of human bladder cancer cells. (A, B) ROS generation and lipid peroxidation in FLRT2‐silenced or CTRL human bladder cancer cells (n = 6). (C, D) Levels of 12/15‐HETEs in cell medium (n = 6). (E, F) Levels of GSH and GPX4 activity in FLRT2‐silenced or CTRL human bladder cancer cells (n = 6). All data are presented as the mean ± SD, p < 0.05 was considered statistically significant. NS indicates no significance.

Fig 5: Overexpression of FLRT2 rescues the vascular aging effect of silencing FLRT2 on endothelial cell senescence.(A–C) HUVECs exogenously expressing empty vector or Flag-FLRT2 were transfected with Con Si or FLRT2 Si. Immunoblot assay was performed with the indicated antibodies (A), and relative cell number (B) and SA-β-Gal activity (C) were assessed at 3 days after siRNA transfection. The values represent the mean ± SD (n = 3; *P < 0.05; **P < 0.01). One-way ANOVA. (D) Representative immunoblot images obtained from aortic lysates of mice injected intravenously with Con Si, FLRT2 Si, empty vector, or Flag-FLRT2 plasmid (n = 5). (E) Image of SA-β-Gal–stained aortas of mice. Scale bar: 5 mm. (F) Immunostaining for p-AKT (S473), p53, and p21 in aortas of mice. Scale bar: 100 μm.