DNMT3B (DNA Methyltransferase 3 Beta)

Notably, recombinant TRAIL protein synergizes with SGI1027 or MS1129 to kill VHL-deficient ccRCC in mice. Collectively, our study unveils an apoptosis induction strategy that involves hijacking HIFs for ccRCC treatment.

Waterpipe smoke may result in a DNA hypomethylation pattern in initial exposure periods, contributing to activate proto-oncogenes and/or genomic instability. Over long periods, it may lead to a methylation pattern similar to that of control or even to hypermethylation, silencing tumor suppressor genes. These alterations in the genome due to hypo/hypermethylation contribute largely for the development of diseases such as oral cancer.

In contrast, HOPX knockdown partially recovered the malignant phenotypes of lung cancer cells treated with SGI-1027 or si-DNMT3B. In conclusion, these findings provide a rationale for targeting DNMT3B-mediated HOPX DNA methylation and identify crucial molecular targets for lung cancer therapy.

The data give insight into how DNA methylation patterns are established in human cells. We discuss these findings and their potential relevance for altered DNA methylation patterns seen in aging tissues and in cancer cells.

Furthermore, supplementation with miR-29b-3p also enhanced the response to immune checkpoint blockade as well as radiotherapy. Taken together, these results suggest a therapeutic approach in which tumor-specific miR-29b-3p increases the benefits of RT by overcoming defective STING in KRAS-mutated CRC patients.

This study demonstrates the therapeutic efficacy of restoring the imbalanced expression of miRNA in the liver. Therefore, the clinical translation of this miRNA-based strategy warrants further investigation.

Our integrated computational and clinical analyses indicate that the piR-823/PIWIL1/DNMT3B/CDH1 axis is a putative epigenetic regulator of EMT and cancer stemness in ovarian cancer. Additionally, piR-823 may serve as a promising prognostic biomarker and therapeutic target, offering novel insights into OC pathogenesis and treatment.

HET-CAM classified the gel as non-irritant. The Puerarin-loaded proniosomal gel represents a promising topical platform with preliminary in vitro antimelanoma cytotoxic potential, warranting additional studies to validate skin delivery, efficacy, and safety.

Notably, the SPAK inhibitor exhibits potent inhibitory effects and synergizes with PD-1 blockade to enhance antitumor efficacy. In summary, these findings establish SPAK as a driver of oncogenesis and immune exhaustion in HCC and highlight dual inhibition as a potential therapeutic strategy.

This study aimed to determine whether the DNMT inhibitor azacitidine (AZA) enhances the antitumor effects of the PARP inhibitor niraparib (NIR) and to identify molecular mechanisms underlying this interaction. OGFR was identified as a novel regulator of HR and PARP inhibitor sensitivity, controlled via noncanonical DNMT3B-dependent transcriptional mechanisms that operate independently of CpG methylation. These findings provide new mechanistic insights into the epigenetic control of DNA repair and support the rationale for combining DNMT and PARP inhibitors as a promising therapeutic strategy for BTC beyond genetically HR-deficient cases.

Furthermore, DNMT3A ablation reduced DNMT3B gene methylation, explaining the down-regulated profiles of genes. Our findings suggest a complex epigenetic regulatory role for DNMT3A, and the compensatory upregulation of DNMT3B in response to DNMT3A deficiency warrants further investigation to be validated in future studies.

Moreover, lactate is taken up and oxidized in mitochondria by the CD147/MCT1/LDHB complex, which correlates with stemness potentials and tumor metastasis in patients with breast cancer. An intracellularly expressed single-chain variable fragment targeting mitochondrial CD147 (mito-CD147 scFv) effectively disrupts the mitochondrial CD147/MCT1/LDHB complex, inhibits lactate-induced stemness potential, depletes circulating breast cancer cells, and reduces metastatic burden, suggesting promising clinical applications in reducing lactate-fueled metastasis.