PDHB (Pyruvate Dehydrogenase E1 Subunit Beta)

The anti-tumor effect of ATF3 inducer 1-targeted upregulation of PER2 combined with copper ionophore elesclomol (ES) was found to be significantly enhanced compared with that of monotherapy in an OSCC xenograft model. These findings reveal a critical role of ATF3-dependent regulation of cuproptosis by PER2 in OSCC development, suggesting targeted upregulation of PER2 or ATF3 in combination to induce cuproptosis as a novel strategy to potentially improve the prognosis of OSCC patients.

Mechanistically, PDHB mediates metabolic reprogramming by binding to the promoter regions of SLC2A1, GPI, and PKM2, promoting glycolysis-related gene transcription, contributes to HCC sorafenib resistance...In summary, our study validates PDHB as an oncogenic drug resistance-related gene capable of predicting HCC tumor progression. PDHB and Isoacteoside could be potential avenues for targeted and combination therapies in liver cancer.

As a member of pan-cancer, PDHB may be a novel cancer marker with potential value in diagnosing cancer, predicting prognosis, and in targeted therapy.

Our study suggested that Metformin may increase the response of cholangiocarcinoma cells to Gemcitabine by suppressing PKM2 to activate mitochondrial apoptosis.

There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence.

Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.

Subsequent studies showed that copper-induced cell death activation could overcome sunitinib resistance in RCC cells. This research illustrated a cuproptosis-related hub gene PDHB which could serve as a potential prognostic marker and provide therapeutic benefits for clinical treatment of ccRCC patients.

Taken together, our study demonstrated the prognostic values of PDHB in pan-cancers. PDHB may be a potential molecular marker to predicting the immune response in cancer patients.

Finally, we conducted in vivo experiments to confirm that HKF promoted CC tumor growth whereas PDHB-AS suppressed CC tumor growth. Collectively, PDHB-AS plays a tumor-suppressive role in the progression of CC, which suggests the therapeutic potential of PDHB-AS for CC.