KDM4B (Lysine Demethylase 4B)

Notable findings include PFD-mediated downregulation of pro-fibrotic miRNAs, hypermethylation of TGFB1, and inhibition of JMJD2B histone demethylase. Together, these findings suggest that PFD not only targets fibrotic and inflammatory pathways but also acts as a novel epigenetic regulator, positioning it as a promising therapeutic candidate for MASLD, MASH, and HCC.

KDM4B inhibits ERα-induced transactivation independent of its Jumanji-C enzyme active region. Taken together, our study suggests that KDM4B acting as ERα co-repressor is involved in the regulation of VC, indicating that KDM4B may be a new potential therapeutic target for VC treatment.

In conclusion, our data highlight that CDYL2b can suppress prostate tumorigenesis, while JMJD2A and JMJD2B may exert their pro-oncogenic functions in part through stifling CDYL2b transcription or CDYL2b activity. In addition, our study revealed that the developmental transcription factors TBX6 and HES7 may also suppress tumorigenesis.

In the context of autoimmune diseases, we found that targeting KDM4B-cGAS axis through either genetic approaches or pharmacological inhibition of KDM4B with JIB-04 effectively ameliorated disease manifestations in both Trex1-deficient mice and peripheral blood mononuclear cells from Aicardi-Goutieres syndrome (AGS) patients. Collectively, this study demonstrated that KDM4B functions as a specific demethylase for cGAS, controlling its chromatin dissociation and subsequent activation, thereby providing a therapeutic rationale for targeting cGAS methylation in human diseases.

Moreover, the aberrant expression of DLX5 in PAX3-FOXO1-driven RMS was regulated by KDM4B/H3K9me2 axis. These findings provided potential therapeutic targets for RMS treatment.

Overall, the present study uncovered a novel function of RSK on the DNA damage response, which provides an additional role of its inhibitor in cancer therapy.

Compared to the FDA-approved anti-melanoma agent dacarbazine, NCGC00244536 exhibited more pronounced cytotoxic and antiproliferative effects in melanoma cells. Importantly, NCGC00244536 demonstrated minimal cytotoxicity to low Kdm4b-expressing mouse embryonic fibroblasts. In conclusion, our findings suggest that KDM4B inhibition can override the antitumor effect of p53, and potentially serve as a therapeutic strategy for melanoma.

A single mutation, R986L, was predicted to significantly affect protein structure using computational modeling. This analysis suggests that KDM4B makes contributions to DSB repair but is not a key player.

The characteristics of circBRAF were examined using divergent PCR primers, Sanger sequencing, fluorescence in situ hybridization (FISH) analysis, and the application of RNase and actinomycin D. The biological function of circBRAF in TNBC was further investigated through colony formation, tube formation, and transwell assays...Furthermore, overexpression of circBRAF was able to overcome the inhibitory effects of siKDM4B and siIGF2BP3 on cell migration and invasion. Our findings suggest that circBRAF may act as an oncogene in TNBC through its specific interactions with KDM4B and IGF2BP3, implying that circBRAF could serve as a potentially effective novel therapeutic target for TNBC.

Overall, this study defined an epigenetic mechanism of UCHL1/KDM4B in activating VEGF signaling. The UCHL1-KDM4B axis represents a novel target for treating ccRCC and improving the efficacy of anti-angiogenesis therapy.

In t(8;21) AML cell lines, WTAP could regulate the expression of KDM4B by regulating the m6A modification of the 3'UTR of KDM4B mRNA, and silencing the expression of KDM4B could inhibit the cellular proliferation in vitro.

In human tumours, KDM4B expression was negatively correlated with clinical outcomes, type I interferon signatures, and responses to immunotherapy. In conclusion, our results demonstrate that targeting KDM4 family can activate tumour-intrinsic innate sensing and immunogenicity, and synergise with immunotherapy to improve antitumour outcomes.