Fig 2: miRNA/mRNA regulatory network analysis. (A) Interaction of the miRNA and mRNA were predicted by TargetScan. The upregulated genes are indicated in pink and red, while the downregulated genes are in green and blue. The relatively credible axes are filtered by TargetScan and miRDB, and further selected by scores. Red regions, blue regions and black lines represented the filtered miRNA/mRNA pathways. (B–D) miR-210-5p/Msln, miR-212-3p/Hmga2, and miR-223-5p/Hpgds axes were preliminarily validated by qRT-PCR. Data were analyzed by unpaired t-test. * p-value of <0.05.

Fig 3: Hpgds is the direct target gene of miR-223-5p. (A) qRT-PCR results revealing miR-223-5p expression of in the corneal epithelium harvested 24 h post-wounding of normal mice (NW group), diabetic mice (DW group), diabetic mice subconjunctivally injected with miR-223-5p antagomir (DW + antagomir group) or antagomir NC (DW + NC group). (B) qRT-PCR results revealing mRNA expression of Hpgds in the corneal epithelium 24 h post-wounding of the same four groups. (C,D) Western blotting showing the protein expression of Hpgds in the cornea 24 h post-injury of these four groups. (E) Schematic representation of the predicted interacting site of mmu-miR-223-5p with Hpgds. (F) Luciferase reporter assay assessed the relative luciferase activity in HEK293T cells transfected with pMIR-REPORT Hpgds-WT-3'-UTR or Hpgds-Mut-3'-UTR upon transfection with miR-223-5p mimic or miRNA mimic NC. (A,B,D) Data were analyzed by one-way ANOVA. If significant, multiple comparations were then performed. (F) Data were analyzed by unpaired t-test. *p-value of <0.05.

Fig 4: Blockade of Hpgds counteracts the beneficial effects induced by miR-223-5p antagomir. (A,B) Western blotting assay showing the protein expression of Hpgds in the cornea 24 h post-wounding of diabetic mice (DW group), miR-223-5p antagomir treated diabetic mice (DW + antagomir group), miR-223-5p antagomir and HQL-79 treated diabetic mice (DW + antagomir + HQL-79 group), miR-223-5p antagomir, and vehicle treated diabetic mice (DW + antagomir + vehicle group). (C,D) Fluorescence staining assay showing the corneal epithelial defect areas of DW group, DW + antagomir group, DW + antagomir + HQL-79 group and DW + antagomir + vehicle group at different timepoints post-injury. (E,F) Corneal whole-mount staining of ß-tubulin III revealing the corneal nerves of each group on day 5 post-wounding. (G) Corneal sensation measurement was conducted on day 5 post-wounding in each group. (B,D,F,G) Data were analyzed by One-way ANOVA. If significant, multiple comparations were then performed. * p-value of <0.05.

Fig 5: GPR44 activation decreases the severity of leukemia(A) CD45.2-recipient mice were maintained on Se-A diet for 4 weeks before retro-orbital transplantation with 1° CD45.1 WT AML donor cells; at 1 week post transplantation, mice were treated i.p. daily with PBS or 0.2 mg/kg CyPGs (DK-PGD2, 15d-PGJ2, ?12-PGJ2, and ?12-PGJ3) for 2 weeks and euthanized after treatment; blood, bone marrow, and spleen were sampled (n = 7–8 in each group).(B) CBC analysis of AML mice at the endpoint in (A).(C) Representative image of spleens isolated from AML mice in (A).(D) Spleen weights (mg) of AML mice in (A).(E and F) Counts of LICs (CD45.1+Lin-Sca-1-c-Kit+, see also Figure S1J) in the bone marrow (E) and spleen (F) of AML mice in (A).(G) 1°-recipient mice were maintained on Se-A diet for 4 weeks before sublethal irradiation (4.75 Gys) and retro-orbital transplantation with GFP BCR-ABL-transduced HSCs; DK-PGD2 (0.2 mg/kg) or PBS control was given daily i.p. starting when peripheral blood WBC is over 5 K/µL for 2 weeks post transplantation. Mice were euthanized after treatment and blood, bone marrow, and spleen were sampled (n = 7–9 in each group).(H) CBC analysis of CML mice in (G).(I) Spleen weights (mg) of CML mice in (G).(J) Weight gain of Se-A CML mice treated with or without DK-PGD2 was expressed as the ratio of after and before treatment (n = 4 in each group).(K and L) Counts of CML cells (GFP+) in the Lin- population in the bone marrow (K) and spleen (L) of CML mice in (G).(M and N) Counts of LICs (GFP+Lin-Sca-1+c-Kit+, see also Figure S3D) in the bone marrow (M) and spleen (N) of CML mice in (G).Data shown are mean ± SEM per group; each dot represents a mouse; *p < 0.05, **p < 0.01.