CBX2 (Chromobox 2)

In this study, EZH2 levels were modulated by CRISPR/Cas9 gene editing and PRC2 activity was inhibited with EZH2 inhibitor EPZ6438 or EED inhibitor MAK683. This was accompanied by increased expression of other PcG genes, including EZH1, CBX2, RING1, EED, and SUZ12, suggesting a compensatory interaction between PRC2 and PRC1 complexes. These findings provide significant clinical relevance, both in elucidating the mechanisms of novel molecular targets and in guiding treatment strategies for lung cancer when using epigenetic inhibitors.

In vitro validation narrowed compounds of interest to raltitrexed, alisertib, GTX-007, LY315920, and PD0325901. Treatment with alisertib leads to decrease in H2AK119ub and shift in the immune tumor microenvironment. Alisertib efficacy in HGSC is dependent on functional CBX2 and cell target engagement confirms selectivity for CBX2, supporting that alisertib activity involves CBX2 inhibition.

CBX2 promotes cisplatin resistance in OC via SIAH2-mediated β-catenin stabilization and ATG9B-dependent autophagy activation. Overall, our study reveals a hitherto undocumented role of CBX2 in mediating DDP resistance, providing insights for potential therapeutic biomarkers to overcome DDP resistance in OC.

Western blot and tube formation assay results showed that CBX2 knockdown, NF-κB activation, METTL3 inhibition, METTL3 overexpression, and SHP2 inhibition all inhibited or promoted angiogenesis. CBX2 promoted oral squamous cell carcinoma via increasing CEP55/NF-κB/METTL3/SHP2 signaling, leading to metastasis, proliferation, and angiogenesis.

In addition, the miR-761 inhibitor reversed the inhibitory effect of si-CASC19 on the biological activity of ovarian cancer cells, while si-CBX2 restored the regulation of miR-761 inhibitor on the development of ovarian cancer. lncRNA CASC19 mediated the malignant progression of ovarian cancer through miR-761/CBX2 axis, which provided a potential therapeutic target for the cure of patients.

CBX2/EZH2 cooperatively confers 5-FU resistance in GC cells through suppressing ferroptosis via H3k27me3, which may lead to a promising therapeutic strategy for GC.

COL6A6 may operate as a tumor suppressor in breast cancer, underscoring its correlation with immune activity in the tumor microenvironment. These findings suggest COL6A6 as a promising therapeutic target and prognostic biomarker warranting further investigation.

Consistency clustering analysis revealed 3 distinct subtypes (C1, C2, C3), with subtype C3 showing elevated activation levels at the majority of immune checkpoints in comparison to subtypes C2 and C1, as well as increased sensitivity to pharmacological agents such as 5-fluorouracil and afatinib. The prognostic assessment model developed in this research offers an innovative approach for the identification of novel prognostic markers in patients diagnosed with (LIHC).

CBX2, CLDN1, SDC2, PGF, FOXS1, ADAMTS18, POLR1B, and PYCR3 were identified as important biomarkers to identify diseased and non-diseased states of gastric cancer; CAVIN2, ADAMTS5, SCARA5, CD300LG, and GIPC2 were identified as important biomarkers for breast cancer; and CLDN18, MYBL2, ASPA, AQP4, FOLR1, and SLC39A8 were identified as important biomarkers for lung cancer. XGB-BIF could be utilized for identifying biomarkers of different cancer types using genetic data, which can further help clinicians in developing targeted therapies for cancer patients.

CG3-46 inhibited the growth of the triple-negative breast cancer cell line MDA-MB-231, accompanied by an increase in the expression of a CBX2 target gene. Our results indicate that CG3-46 represents the first nonpeptide small molecule inhibitor of CBX2, which not only serves as a valuable chemical tool for elucidating the role of CBX2 in cellular epigenetic regulation but also as a starting compound for the development of CBX2-targeted therapeutics for triple-negative breast cancer.

Collectively, these findings suggest the pivotal role of RUNX1-CBX2-MAP4K1 axis in CRC progression and underscore CBX2 as a promising biomarker and therapeutic target. The regulatory function of CBX2 on chromatin accessibility and the role of the RUNX1-CBX2-MAP4K1-pERK axis in the progression of colorectal cancer.

Our findings could provide new perspectives for identifying potential prognostic markers within the CBX family in BC. Targeting CBX2 may present a promising approach to address endocrine resistance in BC therapy.