Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

We have recently reported that type 2 diabetes promotes centrosome amplification via enhancing the expression, biding, and centrosome translocation of rho‐associated coiled‐coil containing protein kinase 1 (ROCK1)/14‐3‐3σ complex in HCT116 cells. In the functional proteomic study, we further investigated the molecular pathways underlying the centrosome amplification using HCT116 cells. We found that treatment of HCT116 cells with high glucose, insulin, and palmitic acid triggered the centrosome amplification and increased the expressions of proliferating cell nuclear antigen (PCNA), nucleophosmin (NPM), and 14‐3‐3σ. Individual knockdown of PCNA, NPM, or 14‐3‐3σ inhibited the centrosome amplification. Knockdown of PCNA inhibited the treatment‐increased expression of ROCK1, whereas knockdown of ROCK1 did not affect the PCNA expression. High glucose, insulin, and palmitic acid also increased the expressions of c‐Jun N‐terminal kinase‐1 (JNK1) and signal transducer and activator of transcription 3 (Stat3), individual knockdown of which upregulated the treatment‐increased expression of 14‐3‐3σ and promoted the centrosome amplification. In contrast, overexpression of JNK1 inhibited the centrosome amplification. Knockdown of Stat3 enhanced the centrosome translocation of 14‐3‐3σ. Moreover, we showed that knockdown of JNK1 inhibited the treatment‐increased expression of Stat3. Knockdown of PCNA, JNK1, or Stat3 did not have an effect on NPM and vice versa. In conclusion, our results suggest that PCNA and JNK1‐Stat3 pathways respectively promotes and feedback inhibits the centrosome amplification by targeting at the ROCK1/14‐3‐3σ complex, and NPM serves as an independent signal for the centrosome amplification.

Accumulating evidence suggests that iron homeostasis is disordered in amyotrophic lateral sclerosis (ALS). In view of the promising performance of epigallocatechin‑3‑gallate (EGCG) in neuroprotection studies, the present study aimed to verify whether EGCG protects motor neurons in an ALS model, and whether it has any effects on iron metabolism using an ELISA and western blotting. The results demonstrated that EGCG decreased oxidative stress and protected motor neurons in the organotypic culture of the rat spinal cord. Furthermore, total iron levels increased significantly in the spinal cord following 3 weeks of treatment with threo‑hydroxyaspartate. In addition, the expression of influx proteins (transferrin receptor and divalent metal‑ion transporter 1) increased significantly. However, EGCG demonstrated no effect on total iron levels and the expression of influx proteins. In conclusion, EGCG leads to a decrease in oxidative stress levels, leading to motor neuron protection in the organotypic culture of a rat spinal cord; however, EGCG does not alter iron metabolism protein expression regulation.

Objective: Diabetes increases the risk for cancers. However, whether it is associated with hematologic malignancies is not clear. The present study investigated the association between diabetes and acute lymphocytic leukemia (ALL), acute myeloid leukemia (ML), non-Hopkin lymphoma (NHL), and multiple myeloma (MM). Methods: Newly diagnosed adult cancer patients were recruited consecutively from our clinical database. Peoples from a local enterprise were recruited to create a small-scale population-based dataset. We compared the diabetes prevalence between the cancer patients and the local people; an increase in diabetes prevalence in the cancer patients suggests an association between diabetes and the cancer(s). Results: We found that the prevalence of diabetes was 19.7%, 21.3%, 12.5%, and 12.0% in ALL, AML, NHL, and MM, respectively, which was higher than that (9.1%) in the local people. Despite that there were more male than female cancer patients, there were more female than male diabetic patients. The increase in diabetes prevalence occurred in ALL and NHL patients aged 18 to 39 years old as well as in AML patients over 40. In MM patients, the increase in diabetes prevalence (18.6%) occurred only in females. Approximately 70% of the diabetic patients were undiagnosed before the diagnosis of the blood cancer. Approximately half of the pre-existing diabetic patients had anti-diabetic treatment, with over 70% of them still had poor glycemic control. Conclusions: Our results suggest that diabetes is associated with ALL, AML, NHL, and MM, at least in adult patients.

Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 expression in LGG patients was significantly associated with poor survival outcomes. Further gene expression analysis revealed that 379 genes were significantly upregulated in LGG samples with high CDKN3 expression, and these genes were primarily involved in the mitotic cell cycle and extracellular matrix organization. Additionally, high CDKN3 expression was closely linked to key signaling pathways such as tumor inflammation, hypoxic response, and tumor proliferation. Immune microenvironment analysis showed that high CDKN3 expression significantly increased the expression of CD4 + T cells and specific immune checkpoint genes, suggesting a potentially poor response to immune checkpoint blockade therapy. Through in vitro and in vivo experiments, we confirmed that CDKN3 silencing significantly inhibited the proliferative capacity of LGG cells. Proteomics revealed that CDKN3 can bind ARG1 and inhibite the intracellular arginase activity. These findings not only improve our understanding of LGG biology but also provide scientific evidence for developing potential therapeutic strategies targeting CDKN3.