ZKSCAN3 (Zinc Finger With KRAB And SCAN Domains 3)

Ultimately, seven key drug targets (SERPING1, TDRD9, GBAP1, FAM241A, ZKSCAN4, ZKSCAN3, Z94721.1) were consistently identified across two MR studies and validated. These targets offer new avenues for LC treatment, highlighting their potential in therapeutic development.

Current therapies include platinum, Taxol, angiogenesis inhibitors, and poly[ADP-ribose]polymerase (PARP) inhibitors...In contrast, expressing exogenous HSPB1 partially rescues the cell proliferation in ZKSCAN3 knockdown cells, which supports HSPB1 as a functional target gene of ZKSCAN3. Collectively, our study uncovers a functional ZKSCAN3-HSPB1 axis that promotes ovarian cancer cell proliferation.

This comprehensive analysis provides a framework for advancing our mechanistic understanding of ZKSCAN3 and its implications in human health and disease. This review synthesizes recent advances in elucidating the regulatory networks and functional complexity of ZKSCAN3, highlighting its dual roles in physiological and pathological contexts.

Meanwhile, ERK1/2 and Smad1 signaling pathways might be related to function of OC-2 driving tumor aggressiveness. We revealed that OC-2 might regulate tumor growth, metastasis, angiogenesis via ERK1/2, Smad1 signaling pathways and regulate VEGFA expression for tumor angiogenesis via activating ZKSCAN3 transcriptional program, indicating that OC-2 was a convincing target to develop novel anti-tumor drugs based on angiogenesis.

In addition, our study revealed that ALKBH5-ZKSCAN3-VEGFA signaling was significantly activated during MNNG-induced gastric carcinogenesis, and further studies in gastric cancer patients showed that ALKBH5, ZKSCAN3, and VEGFA expression were upregulated in cancers compared with paired gastric mucosal tissues, that ALKBH5, ZKSCAN3, and VEGFA could serve as important biomarkers for determining patient prognosis, and that the molecular combination showed greater prognostic value. These findings provide a theoretical basis for developing gastric cancer interventions for NOCs and for determining gastric cancer progression.

Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.

In contrast, using the liver-derived Hep3B cells, 71.6% residual activity could be measured. This indicates that the transcription factors ZKSCAN3 and SOX9 are important for the cell type-specific transcriptional regulation of the Ct-SLCO1B3 gene.

Furthermore, despite the severe impact on fork structure and chromosomal stability, depletion of ZKSCAN3 did not affect the short-term survival of BRCA1-proficient or -deficient cells after treatment with cancer drugs hydroxyurea, PARPi, or cisplatin. Our findings reveal a unique relationship between ZKSCAN3 and BRCA1 in fork protection and add to our understanding of the relationships between replication fork protection, chromosomal instability, and chemosensitivity.

Their IHC scores were considerably different (61.4 in NM; 88.4 in HPP; 189.6 in AD; 246.9 in AC). In conclusion, ZKSCAN3 could be responsible for WNT/β-catenin-induced chromosomal instability in colon cancer cells through the suppression of MAD2L2 expression.