Cellular Oncology最新文献

Purpose: The selective induction of nucleolar stress in cancer cells has become a potential anticancer therapy. However, precisely regulating the key molecules involved in nucleolar stress remains a challenging topic in current research. ENY2 transcription and export complex 2 subunit (ENY2) is a transcription-associated nuclear protein that is upregulated in several cancers. However, its specific function and mechanistic role in oncogenesis remain poorly characterized and require further exploration.

Methods: ENY2 was identified by screening ChIP-seq and public databases. Its role in tumor development was confirmed through in vivo and in vitro experiments. RNA sequencing, polysome profiling, agarose gel electrophoresis, and immunofluorescence suggested ENY2's involvement in ribosome biogenesis. Interacting proteins were identified by confocal microscopy, co-IP, and molecular docking, then validated by western blotting and ubiquitination assays. Finally, drug resistance experiments evaluated ENY2's clinical potential.

Results: We discovered that the overexpression of ENY2 significantly enhances tumor growth and cell cycle progression both in vitro and in vivo. Conversely, depletion of ENY2 facilitating the release of NPM1 into the nucleoplasm, thereby impeding ribosomal subunit export and inducing nucleolar stress. Additionally, the released NPM1 interacts with MDM2 within the nucleus to stabilize p53 protein levels, consequently inhibiting tumor growth. Notably, knockdown of ENY2 in p53-mutant cancer cell lines exhibits an augmented binding affinity and silencing efficacy of RISC towards target mRNA molecules, ultimately suppressing tumor proliferation through a p53-independent manner.

Conclusions: This study elucidated a previously unrecognized role of ENY2 in tumor growth, clarified the NPM1/MDM2/ p53-dependent mechanism of ENY2-mediated tumor cell growth suppression. We also provided a novel p53-independent RISC-IL11 nucleolar stress response pathway, which may provide a new target for the treatment of breast cancer.

Background: Nasopharyngeal carcinoma (NPC), as a cancer type highly sensitive to radiotherapy, has radiation therapy as the preferred clinical treatment strategy. However, acquired radioresistance poses a significant challenge to the overall therapeutic efficacy for NPC patients.

Methods: In this study, we established two radioresistant NPC cell lines, CNE2-IR and HONE1-IR.

Results: RNA sequencing analysis revealed that CCNA1 was upregulated in both radioresistant NPC cell lines. Downregulation of CCNA1 enhanced the radiosensitivity of these two radioresistant NPC cell lines. Further research found that CCNA1 expression was induced and upregulated during radiotherapy and was associated with poor prognosis in NPC patients. Through in-depth mechanistic studies, we confirmed that CCNA1 may influence radiosensitivity through ROS antioxidant stress and anti-apoptotic signaling. High expression of CCNA1 enhanced NPC cell viability and inhibited apoptosis, while downregulating CCNA1 improved the radiosensitivity of NPC cells. The mechanism of radiosensitization was primarily mediated by the AKT/mTOR pathway.

Conclusions: These findings suggest that CCNA1 could serve as a potential predictive biomarker for radiosensitivity in NPC patients, providing new insights for developing personalized comprehensive chemoradiotherapy strategies for NPC patients.