ALKBH2 (AlkB Homolog 2)

The results imply that, at least in isolated form, FTO preferentially acts as a hydroxylase, producing a hemiaminal product, rather than a demethylase, distinguishing it from ALKBH5. They highlight a need for investigations into the roles of hemiaminal-type modifications to nucleic acids, in both healthy biology and disease.

Collectively, our results uncover a new and direct role for USP7 in MGMT-mediated direct reversal repair and TMZ resistance, positioning USP7 as a distinctive integrator of alkylation repair pathways. Targeting USP7 provides mechanistic insights into regulating diverse alkylation repair pathways and offers a strategy to enhance the efficacy of combination chemotherapies, including TMZ and other alkylating agents, by modulating distinct repair mechanisms in GBM.

ALKBH2 overexpression is observed in many cancer and leads to temozolomide resistance in glioblastoma cell lines...Building on our previously reported finding that the HIV protease inhibitor ritonavir selectively binds and inhibits ALKBH2, we synthesized a BODIPY-labeled ritonavir (rit-BD) as an imaging agent...Furthermore, In vitro and in cellulo experiments and live-cell imaging confirmed that rit-BD could be used to label ALKBH2 in the living cell nucleus. Our findings establish rit-BD as a unique dual-purpose agent for visualizing ALKBH2 dynamics and inhibiting DNA repair activity in cancer cells.

The data indicate that ALKBH2 protects against the anticancer effect of ART, and the mutation of IDH1/2 commonly occurring in low-grade gliomas sensitizes to ART via an ALKBH2-dependent mechanism. The data support the use of ART in the therapy of IDH1/2-mutated cancers both in combination with chemotherapy and adjuvant treatment.

TP53 and BRCA2 GPVs and the ALKBH2 novel variant are associated with early-onset LADC in Asians.

Genome-wide methylome analysis of cells chronically treated with NO (10 days) shows enrichment of 5mC and 5hmC at gene-regulatory loci, correlating with altered expression of NO-regulated tumor-associated genes. Regulation of DNA methylation is distinctly different from canonical NO signaling and represents a unique epigenetic role for NO.

These results highlight the regenerative role of NMN in mouse and human oocytes exposed to the deleterious effects of chemotherapy and aging, representing a potential therapeutic alternative for fertility preservation and aged patients seeking to achieve motherhood with autologous oocytes.

Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.

We discovered dynamically regulated patterns of ALKBH2 and ALKBH3 gene expression in patients infected with HTLV-1, and specific CpG sites epigenetically regulated by HTLV-1 infection. This study provides novel insights into HTLV-1 infection and contributes to the elucidation of ATL pathogenesis.

Our findings indicate that functional promoter variants in DDR genes, in addition to protein-truncating variants, can be pathogenic and contribute to lung cancer susceptibility.

In addition, AH2-14c exhibited much better activities of anti-viability, anti-proliferation and anti-migration against U87 cells. Collectively, we discovered the first potent and selective ALKBH2 inhibitor, which could be taken as a foundation for future drug development and mechanism of action studies.

Interestingly, we observed that one of the inhibitors, ritonavir, could inhibit ALKBH2-mediated DNA repair significantly via competitive inhibition and sensitized cancer cells to alkylating agent methylmethane sulfonate (MMS). This work may provide new insights into the possibilities of utilizing HIV protease inhibitor ritonavir as a DNA repair antagonist.