HCFC1 (Host Cell Factor C1)

Mechanistic studies integrating RNA sequencing, flow cytometry, and western blot analysis showed that PCTM inhibited the proliferation and progression of bladder cancer cells by downregulating CDC42 and HCFC1 and indirectly inhibiting the expression of the cell-cycle protein A1, which subsequently induced S-phase arrest of mitosis. Taken together, these findings suggest that the PCTM microspheres may be a promising intravesical therapeutic agent for bladder cancer tumor eradication, thus providing a transformative strategy to significantly improve the prognosis of patients with NMIBC.

In addition, we demonstrated that BAP1-mediated regulation of gene expression and ferroptosis is dependent on ASXL family members instead of other BAP1-associated factors like FOXK1/2, HCFC1, and OGT. Together, our findings uncover a previously unappreciated epigenetic mechanism underlying the regulation of ACSL4 by H2A monoubiquitination, which connects ACSL4-mediated lipid metabolism to ferroptosis driven by BAP1, providing new insights into the understanding of metabolic regulation of BAP1-related diseases such as cancers.

The results emphasize the clinical relevance of integrating multi-layered analyses of miRNA-protein interactions. The observed associations highlight the role of these molecular markers in tumor progression and patient survival and offer promising opportunities for future research and clinical application in precision oncology.

Cytarabine, daunorubicin, and etoposide (ADE) have been the standard backbone of induction chemotherapy regimens for acute myeloid leukemia (AML) patients for over five decades. We identified seveal mediators that would represent clinically and biologically significant genes for ADE treatment, such as BCL2, CLIP2, and VAV3, which are resistant genes with high expression associated with poor outcomes in pAML treated with ADE, and GRPEL1, HCFC1, and TAF10, which are sensitive genes with high expression showing beneficial outcomes. Notably, knockdowns of the BCL2, CLIP2, and VAV3 genes sensitize the ADE component in AML cell lines, suggesting that these genes should be further studied as potential therapeutic targets to overcome chemoresistance.

Blocking MDVs formation with the microtubule inhibitor nocodazole (NOC) activates the HCFC1-TFEB-LC3 axis, weakens HSP90 inhibitors-induced MDVs and the release of MDVs-derived EVs, inhibits the growth of tumor cell spheres and primary liver tumors, and reduces the extravasation of cancer cells to secondary metastatic sites. Taken together, these data suggest that combination therapy should be used to reduce the metastatic risk of low TFEB-triggered-MDVs formation caused by HSP90 inhibitors.

The MD signature has the capacity to significantly contribute to the prediction of personalized outcomes and the advancement of novel therapeutic strategies tailored for GC patients.

Mechanistically, we found that OGT-dependent cleavage of host cell factor C1 (HCF-1) is required for the avoidance of GIN and IFN-I production in tumors. In summary, our results identify OGT-mediated genomic stability and activate cGAS-STING pathway as an important tumor-cell-intrinsic mechanism to repress antitumor immunity.

Associations involving the essential gene signature of breast cancer metastasis indicate true biological changes intrinsic to cancer cells, with important implications for applying existing therapies or developing alternate therapeutic approaches.

This suggests that a subset of cases may be attributable to fusion products among genes that are not covered by the assay, or perhaps altogether different molecular mechanisms. In all, these findings confirm that RNA-Seq is a potentially useful ancillary test in the diagnosis of endometrial stromal neoplasms and highlight their diverse morphology.

Conclusions HCFC1, as a co-transcription factor, can enhance its transcriptional function by interacting with YY1, and further regulate the transcription of immune checkpoint molecules PD-1. FOXM1D inhibits the nuclear entry of HCFC1 by interacting with the N-terminus of HCFC1, attenuates the transcriptional activation of YY1 by HCFC1, and then inhibits the transcription of various immune checkpoint molecules such as PD-1.