DDB2 (Damage Specific DNA Binding Protein 2)

Mechanistically, inhibition of HDAC6 disrupted its interaction with DNA damage repair proteins (DDB2 and DEK) and suppressed gene expression in the DNA damage repair pathway, leading to the accumulation of irradiation-induced DNA damage and tumour regression. Our findings establish HDAC6 as a predictive biomarker for radiation response in melanoma and demonstrate that pharmacological inhibition of HDAC6 with WT-161 could expand the clinical utility of radiotherapy in patients with UM.

Progesterone and adiponectin receptor 3 (PAQR3) is a Golgi-localized seven-transmembrane protein that anchors rapidly accelerated fibrosarcoma kinase (Raf) and suppresses rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (Ras/Raf/MEK/ERK) signaling, thereby influencing cellular proliferation, differentiation, and metastasis...These effects are modulated by upstream regulators, including microRNA-543 (miR-543), circular RNA 0043280/microRNA-203a-3p (circ_0043280/miR-203a-3p), microRNA-15b (miR-15b), human epidermal growth factor receptor 2 (HER2), 5-aza-2'-deoxycytidine (5-Aza-CdR), autophagy-related 7 (ATG7), and damage-specific DNA binding protein 2 (DDB2). In conclusion, PAQR3 functions as a tumor suppressor and holds potential as a prognostic biomarker. Targeting PAQR3-related pathways may provide new therapeutic opportunities.

Taken together, the present study demonstrates that DDB2 promotes EMT by activating the NF-κB pathway in GBM. These findings provide new insights into the role of DDB2 in GBM, suggesting that DDB2 could serve as a potential therapeutic target and prognostic marker for this malignancy.

A further study showed that quercetin upregulates the expression of p53 by regulating the lncRNA DDB2-AS1/miR-4728-5p pathway, thereby inducing ferroptosis in cisplatin-resistant NSCLC cells, thus overcoming cisplatin resistance. These findings demonstrate that quercetin induces ferroptosis through the DDB2-AS1/miR-4728-5p/p53 axis, thereby reversing cisplatin resistance in NSCLC, and highlighting its potential as an effective adjuvant in NSCLC chemotherapy.

Furthermore, loss of FTO reduced tumor growth in mice and FTO expression was upregulated in cutaneous squamous cell carcinoma (cSCC) compared with normal skin. Together, these findings uncover a critical role for FTO in regulating post-transcriptional gene expression in the UVB damage response and suggest that FTO may be a therapeutic target in skin cancer.

None of the animals revealed the expected DGE pattern corresponding to a moderate to high H-ARS-severity degree. Hence, the Göttingen minipig did not qualify as another validation model for our specific gene set, which does not argue against their validity for other purposes.

XP-C was the predominant subtype, followed by XP-E in patients with XP with ocular involvement. XP-E subtype has been reported for the first time in Indian data in this study. Most variants were frameshift or stop gain. The patients with XP-E subtype may be more at risk of OSN development. These findings underscore the importance of routine ocular surveillance and genetic testing in XP.

Co-treatment with lapatinib and doxorubicin exhibited synergistic cytotoxicity in both cancer cell lines and patient-derived organoids. These findings reveal a previously unrecognized role for lapatinib in targeting DNA repair machinery, supporting its repurposing as a chemosensitizing agent. Our study highlights DDB2 as a critical mediator of chemoresistance and proposes disruption of DDB2-dependent DNA repair as a novel strategy for chemosensitization.

Additionally, across all target-source configurations, electrons were the primary contributors to DNA damage, while photon emissions had the lowest impact. The findings of present study highlight that 161Tb can be a better candidate than 177Lu, particularly for treating the single and cluster tumor cells.

We also discuss miRNAs (such as miR-519a-3p, let-7e, miR-216b), which affect responses to OvCa therapy by targeting PARP1 (Poly(ADP-Ribose) Polymerase-1). Finally, we also discuss why, despite the identification of multiple miRNAs capable of regulating DNA repair genes, as well as those involved in the response to therapy, no miRNA-based drugs have been approved for OvCa treatment in clinics.

Mechanistically, RNA sequencing revealed that 17a downregulated the nucleotide excision repair (NER) and NF-κB pathways, suppressing expression of NER-related genes (ERCC2, POLE2, LIG1, GTF2H3, and DDB2) at mRNA and protein levels and inhibiting phosphorylation of IKKα and p65. These findings position 17a as a potent therapeutic candidate for TNBC treatment, warranting further clinical investigation.

Altogether, our work uncovers new insights into the link between TFHDW and the PIAS4/STAT3/AR axis in prostate cancer. These findings may provide a novel therapeutic option for targeting the PIAS4/STAT3/AR axis in prostate cancer.