Fig 2: Inhibition of HDAC7 rescues the function of miR-143 deficiency in mice.qRT-PCR analysis (a) of the relative expression levels of HDAC7 and western blot analysis (b). qRT-PCR analysis (c) of the relative levels of HDAC7 and Western blot analysis (d) of HDAC7 and GADPH in BMSCs derived from WT, miR-143 knockout mice transfected with HDAC7-siRNA, and miR-143-knockout male mice (n = 8 per group). Microcomputed tomography images (e) of trabecular bone microarchitecture in femora and quantitative microcomputed tomography analysis (f) of trabecular bone microarchitecture from miR-143-knockout mice injected with cholesterol-conjugated control RNA or HDAC7-siRNA in the tail vein (n = 8 per group). Scale bar: 100 μm. g, h Representative images of calcein double labeling of trabecular bone (g) with quantification of the BFR per bone surface (BFR/BS) (h left) and the mineral apposition rate (MAR) (h right) (n = 8 per group). Scale bar: 100 μm. i Representative images of CD31 (green), Emcn (red) immunostaining from miR-143-knockout mice injected with cholesterol-conjugated control RNA or HDAC7-siRNA in the tail vein. Scale bar: 100 μm. j FACS analysis dot plot of CD31hiEmcnhi endothelial cells from miR-143-knockout mice injected with cholesterol-conjugated control RNA or HDAC7-siRNA in the tail vein. Data are reported as the mean ± SD. *p < 0.05, **p < 0.01. Data are representative of three independent experiments.

Fig 3: Inhibition of HDAC7 depresses cancer cell growth in vivo. (A) NOD‐ Prkdcscid IL2rgtm1 /Bcgen mice were orthotopically injected with ES2 cells (1 × 106 cells/mouse in 150 μL volume), which were infected with the indicated lentiviral vectors. Tumour volumes were measured by vernier calliper every 3 days until the end of the experiment; (B) The tumours were isolated and pictured (right) and tumour weight (left) was calculated in control group and HDAC7 KO group (n = 6 mice/group) for 30 days after injected; (C) A schematic model shows that HDAC7 facilitates ovarian cancer cell proliferation and invasion by activating PI3K/AKT/mTOR signalling; The data were expressed as mean ± standard deviation and analysed by the t test (*p < 0.05; **p < 0.01; ***p < 0.001).

Fig 4: HDAC7 is upregulated in ovarian cancer and high HDAC7 expression correlates with poor prognosis. (A) Representative images of HDAC7 IHC staining and (B) H‐scores (mean ± SD) in sections of fallopian tube (n = 5) and ovarian tumours (n = 5), each group from the same patient; (C) Kaplan–Meier analysis the effect of HDAC7 on survival in ovarian cancer; The cell experiment was repeated 3 times. The data were expressed as mean ± standard deviation and analysed by the t test (*p < 0.05; **p < 0.01; ***p < 0.001).

Fig 5: Epigenetic modifiers increase γδ T cell treatment efficacy. (A) Dose–response curves of bicellular A375‐fibroblast spheroids, A2058‐fibroblast spheroids, patient derived melanoma spheroids and melanoma patient‐derived organoids (MPDOs) after treatment with Entinostat, Decitabine, JQ‐1, Tubastatin A, Valproic acid, Ricolinostat, Vorinostat and DMSO controls for 3 days. Values represent mean ± SEM, n = 4. (B) Expression of MICA/B, FasL, PD‐L1 and PD‐L2 in cells from A2058‐fibroblast spheroids was measured by FACS after Entinostat, Decitabine, JQ‐1, Tubastatin A, Valproic acid, Ricolinostat and Vorinostat treatment (5 μM) for 48 h. *p < 0.05. **p < 0.01. (C) Western blot analysis of HDAC6, HDAC7, COX2, phospho‐STAT3, total STAT3, phosphor‐ERK, total ERK, phospho‐JNK, total JNK and GAPDH proteins in A2058‐fibroblast spheroids after Entinostat, Decitabine, JQ‐1, Tubastatin A, Valproic acid, Ricolinostat and Vorinostat treatment (5 μM) for 48 h (left panel). Densitometry quantification of the HDAC7, HDAC6 and COX2 (right panel). **p < 0.01. (D) NKG2A, PD‐1, NKG2D, CXCR3. CD107a and intracellular IFN‐γ in γδ T cells was measured by FACS after Entinostat, Decitabine, JQ‐1, Tubastatin A, Valproic acid, Ricolinostat and Vorinostat treatment (5 μM) for 48 h. *p < 0.05. **p < 0.01. (E) Cytotoxic function of γδ T cells against A2058‐fibro spheroids and MPDOs combined with 1 μM of Entinostat, Decitabine, JQ‐1, Tubastatin A, Valproic acid, Ricolinostat, Vorinostat and DMSO controls. n = 4. *p < 0.05. **p < 0.01