a-flow-cytometry-based-method-for-profiling-immune-cells-human-blood

A Flow Cytometry-Based Method for Profiling Immune Cells in Human Blood and Tumors

Flow cytometry enables the simultaneous characterization of multiple immune-cell populations and their phenotypic subsets in clinical specimens. However, ...

Luoyang Central Hospital Affiliated to Zhengzhou University

Primary adenosquamous carcinoma (ASC) of the lung is a rare and aggressive disease. The accurate diagnosis of ASC based on small biopsies is challenging because of the mixed components within the tumor, and this may lead to suboptimal treatment. Furthermore, information about the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung ASC is limited.

Surgical significance and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in patients with primary lung adenosquamous carcinoma.

Chemoresistance is a major obstacle faced by oesophageal cancer patients and is synonymous with a poor prognosis. MCL1 is a pivotal member of the anti-apoptotic Bcl-2 protein family, which has been found to play an important role in cell survival, proliferation, differentiation and chemoresistance. Thus, it might be an ideal target for treating oesophageal cancer patients. Although it is known that MCL1 is degraded via the ubiquitin-proteasome system, the deubiquitylating enzyme (DUB) responsible for stabilizing MCL1 remains elusive to date. Herein, we demonstrate that Ubiquitin-Specific Protease 20 (USP20) is a novel regulator of the apoptotic signaling pathway. Moreover, USP20 could regulate the deubiquitination of MCL1 to, in turn, regulate its stability. Increased expression of USP20 was correlated with increased levels of MCL1 protein in human patient samples. In addition, depletion of USP20 could increase the polyubiquitination of MCL1, thereby increasing the conversion rate of MCL1 and the sensitivity of cells to chemotherapy. Overall, our findings indicate that the USP20-MCL1 axis might play a key role in the apoptotic signaling pathway.

The deubiquitinating enzyme USP20 regulates the stability of the MCL1 protein.

Many cancers exhibit resistance to chemotherapy, resulting in a poor prognosis. The transcription factor NRF2, activated in response to cellular antioxidants, plays a crucial role in cell survival, proliferation, and resistance to chemotherapy. This factor may serve as a promising target for therapeutic interventions in esophageal carcinoma. Recent research suggests that NRF2 activity is modulated by ubiquitination mediated by the KEAP1-CUL3 E3 ligase complex, highlighting the importance of deubiquitination. However, the specific deubiquitinase responsible for regulating NRF2 in esophageal cancer remains unknown. In this study, a novel regulator of the NRF2 protein, Ubiquitin-Specific Protease 35 (USP35), has been identified. Mechanistically, USP35 modulates NRF2 stability through enzymatic deubiquitination. USP35 interacts with NRF2 and facilitates its deubiquitination. Knockdown of USP35 leads to a notable increase in NRF2 levels and enhances the sensitivity of cells to chemotherapy. These findings suggest that the USP35-NRF2 axis is a key player in the regulation of therapeutic strategies for esophageal cancer.

Article	Year
Surgical significance and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in patients with primary lung adenosquamous carcinoma. Cancer management and research\| PubMed ID: 30122989	2018
The deubiquitinating enzyme USP20 regulates the stability of the MCL1 protein. Biochemical and biophysical research communications\| PubMed ID: 35063767	2022
The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein. Open life sciences\| PubMed ID: 39156988	2024

Dian Zhang

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