Oral squamous cell carcinoma (OSCC) is highly invasive malignancy with limited effective therapeutic strategies. Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like molecule that has been implicated in several cancers; however, its role in ferroptosis within OSCC remains unclear. In this study, UFM1 was demonstrated to be upregulated in OSCC. UFM1 depletion suppressed proliferation and dissemination of OSCC cells and induced ferroptosis characterized by increased lipid peroxidation and Fe2+ accumulation. Mechanically, UFM1 deficiency significantly reduced SLC7A11 levels and sensitized cells to oxidative stress. Reintroduction of SLC7A11 rescued ferroptosis and restored cell survival in UFM1-deficient cells. In vivo, UFM1 depletion significantly inhibited tumor growth, reduced SLC7A11 expression, and increased lipid oxidation, as indicated by 4-hydroxynonenal (4-HNE) immunohistochemical staining. These findings suggest that UFM1 protects OSCC from ferroptosis by stabilizing SLC7A11 protein via UFMylation, thereby preventing its proteasomal degradation.

Glioma is the most aggressive tumor of the central nervous system and is associated with poor prognosis, especially in patients with high-grade gliomas. In this study, we investigated the biological role of inhibitor of kappa B kinase interacting protein (IKBIP) in promoting the progression of glioma. Analysis of the TCGA and GTEx databases revealed that IKBIP is upregulated in both lower-grade gliomas (LGG) and glioblastomas (GBM) compared with normal brain tissues. Kaplan-Meier survival analysis demonstrated that IKBIP upregulation is associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with LGG. Pan-cancer analysis indicated that IKBIP is aberrantly expressed in various malignant tumors, including gliomas. IKBIP knockdown inhibited the proliferation of glioma cells both in vitro and in vivo. Additionally, IKBIP knockdown in U251 and U87 glioma cell lines significantly suppressed their invasive capacity. Furthermore, IKBIP knockdown resulted in decreased expression of proteins associated with Wnt/β-catenin/epithelial-mesenchymal transition (EMT) pathway, including β-catenin, ZEB1, ZEB2, N-cadherin, whereas the expression of E-cadherin was increased. Conversely, IKBIP overexpression reduced the level of phosphorylated β-catenin (p-β-catenin) while increasing the expression of total β-catenin in glioma cells. Furthermore, we identified that transcription factor SP1 (Specificity Protein 1), which is also upregulated in glioma tissues and cell lines and is associated with the malignant phenotype of glioma, can bind to the promoter region of IKBIP. Upregulation of SPI in glioma cells significantly increased the expression level of IKBIP, while inhibiting the phosphorylation of β-catenin. These findings collectively suggest that upregulation of IKBIP promotes the proliferation and invasive behaviors of glioma cells by activating the Wnt/β-catenin/EMT pathway. Overall, our findings suggest that SP1-IKBIP axis facilitates the proliferation and invasion of glioma through Wnt/β-catenin-associated EMT, and SP1-IKBIP axis may represent a promising target for the clinical diagnosis and treatment of glioma.

Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer (GC). Although autophagy is involved in H. pylori infection, its role in H. pylori-associated tumorigenesis remains unclear. Here, we investigated whether enhancing autophagy suppresses GC malignancy under H. pylori infection. Autophagy and mitochondrial markers were analyzed in GC tissue microarrays and the TCGA-STAD dataset. Functional studies employed H. pylori (strain 49503)-infected GC cell lines and xenograft models, with autophagy manipulated by pharmacological induction, Atg5 knockout, gene silencing, or overexpression. Molecular and cellular analyses included Western blotting, luciferase reporter assays, RNA sequencing, transmission electron microscopy (TEM), mitochondrial function tests, and additional functional assays. We observed elevated levels of LC3 and p-Drp1 in tumor tissues. H. pylori infection increased autophagy, cell migration, sphere formation, and transient tumor growth, while reducing cell viability and colony formation; autophagy induction suppressed these malignant features. TEM revealed abundant autophagy-like vesicles and mitochondrial alterations in infected cells. Mechanistically, H. pylori activated the Erk1/2 and JNK signaling pathways to induce autophagy while inhibiting other oncogenic signaling pathways. Notably, although H. pylori induces robust autophagy, further enhancement of this process using autophagy inducers attenuated gastric cancer malignancy, suggesting that further pharmacological modulation of autophagy warrants evaluation as a potential therapeutic strategy.

Mitochondria-related genes or proteins can affect various functional indicators of mitochondria, encompassing ATP synthesis, the generation of reactive oxygen species, and the intricate process of mitochondrial autophagy. Numerous researches have unveiled a profound association between mitochondrial dysfunction and the onset, progression, and prognosis of hepatocellular carcinoma. In recent years, a large number of studies have conducted experiments on mitochondria-related genes or proteins to explore their roles and mechanisms in causing mitochondrial functional changes and thereby influencing the progression of hepatocellular carcinoma. Over the past five years, a plethora of studies have been meticulously conducted on mitochondria - related genes and proteins. The aim is to precisely define their functions and the underlying molecular mechanisms in triggering mitochondrial functional aberrations, thereby affecting the progression of HCC. This review is dedicated to comprehensively recapitulating the pertinent progress made in the past half - decade. Additionally, it will delve into how these factors can present feasible and prospective therapeutic modalities for the management of HCC.

The role and efficacy of consolidative radiotherapy (CRT) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with first-line chemo-immunotherapy remain to be clarified. In this retrospective cohort study, we divided mNSCLC patients who achieved disease control with initial chemo-immunotherapy into CRT and non-CRT groups. Propensity score matching was employed to balance baseline characteristics. Results showed that the median overall survival (OS) was significantly longer in the CRT group (38.5 months) compared to the non-CRT group (25.1 months) (HR=0.48, P=0.004). Similarly, median progression-free survival (PFS) was 16.2 months in the CRT group versus 9.8 months in the non-CRT group (HR=0.52, P=0.005). CRT was identified as an independent favorable prognostic factor, with OS benefits consistent across all subgroups. Safety analysis revealed no significant difference in the incidence of grade ≥3 adverse events between the groups. These findings indicate that consolidative radiotherapy following first-line chemo-immunotherapy is associated with significantly improved survival outcomes in mNSCLC patients, demonstrating a favorable risk-benefit profile in real-world practice.

Ubiquitin-conjugating enzyme E2W (UBE2W), a member of the ubiquitin-conjugating enzyme family, is highly expressed in pancreatic cancer (PC). However, the biological function of UBE2W in cancer, particularly in human PC, remains poorly understood. This study aimed to elucidate the molecular mechanism by which UBE2W regulates the initiation and progression of PC. Integrating multiple databases and validating with clinical samples, the study identified that UBE2W is significantly overexpressed in PC tissues. High UBE2W expression is closely associated with shortened overall survival, disease-specific survival, and disease-free survival in patients. In vitro and in vivo functional experiments demonstrated that UBE2W overexpression promotes the proliferation and migration of PC cells while inhibiting apoptosis. Conversely, UBE2W knockdown significantly reduces cell viability, induces apoptosis, and suppresses tumor growth in vivo. Mechanistically, UBE2W mediates K63-linked ubiquitination of p53, regulates p53 subcellular localization, and thereby impairs p53-mediated DNA damage repair and apoptotic pathways. Collectively, UBE2W inhibits the tumor-suppressive function of p53 and promotes PC progression through the aforementioned mechanism. Targeting the UBE2W-p53 axis provides a novel therapeutic strategy for PC, and the development of related inhibitors holds promise for improving patient prognosis.

Lung adenocarcinoma (LUAD) exhibits poor prognosis partly due to dysregulated calcium signaling. Here, we integrated bulk RNA-seq (TCGA/LUAD, n = 440) and single-cell sequencing (GSE131907) to identify calmodulin-related prognostic genes. Differential expression analysis and LASSO-Cox regression identified SPHK1 and ASPM as independent predictors of overall survival (HR = 1.52/1.47, P < 0.001). A risk model incorporating these genes stratified patients into high/low-risk groups with distinct clinical outcomes (3-year AUC = 0.83). High-risk patients showed elevated γδ T cells and TIDE scores, while SPHK1/ASPM expression correlated with an immunosuppressive myeloid phenotype and M2-like polarization. Single-cell analysis revealed SPHK1+-ASPM+ myeloid cells dominated in early differentiation stages, with pseudo-time trajectories indicating SPHK1 downregulation and ASPM upregulation during myeloid maturation. Multiplex immunofluorescence validated co-localization of SPHK1/ASPM with MPO+ myeloid cells in tumor tissues. Importantly, the MPO+SPHK1+/ASPM+ myeloid compartment was significantly enriched in anti-PD-1 non-responders (P < 0.05). Our study establishes a calcium signaling-based prognostic signature, uncovers myeloid SPHK1/ASPM as drivers of immunosuppression, and provides a potential biomarker for immunotherapy stratification.

This study examined the antitumor effects and molecular mechanisms of isorhamnetin in glioma treatment with a particular focus on its regulation of the PI3K/Akt signaling pathway, for developing targeted therapies. Using network pharmacology, we identified isorhamnetin could be used as a potential active ingredient in the regulation of glioblastoma (GBM) through the PI3K/Akt pathway. Bibliometric analysis was then used to review the current state and the developing trends in isorhamnetin research for anti-tumor applications. It was confirmed that isorhamnetin exerts its effects via the PI3K/Akt pathway. Our in vitro experiments showed further that isorhamnetin inhibits the proliferation and migration of glioma cells in a dose-dependent manner. Furthermore, isorhamnetin downregulated proteins related to the PI3K/Akt pathway, thereby suppressing its signaling activity. Isorhamnetin has antitumor effects against glioma by modulating the PI3K-Akt signaling pathway, providing experimental and mechanistic evidence for the potential use of isorhamnetin as a complementary GBM therapy.

Lymph node metastasis (LNM) is a key factor in the recurrence and progression of papillary thyroid carcinoma (PTC). Phosphodiesterase 4C (PDE4C) serves as a crucial regulator in cancer development and metastasis, its functional role and mechanism in LNM of PTC need further elucidation. PDE4C and embryonic lethal abnormal vision like 1 (ELAVL1) expression in PTC and adjacent normal tissues were assessed using bioinformatic analysis and immunohistochemistry (IHC). We found that PDE4C and ELAVL1 were upregulated in PTC tissues. Cell viability in BCPAP and TPC-1 cell lines was assessed via cell counting kit-8 (CCK-8) assay, while Transwell assays were employed to determine their migratory and invasive capacities. Our data revealed that silencing of PDE4C remarkably suppressed BCPAP and TPC-1 cell proliferation, migration and invasion. Besides, the association between ELAVL1 and PDE4C was predicted and verified by ENCORI, RNA pull down and RNA immunoprecipitation (RIP) assay. The mRNA of ELAVL1 and PDE4C were evaluated via quantitative real-time PCR (qRT-PCR). ELAVL1 and PDE4C expression was examined using Western blot analysis. The number of metastatic tumors in the lymph nodes was assessed by hematoxylin-eosin (HE) staining. Ki-67 level in tumor tissues were determined by IHC. ELAVL1 interacts with PDE4C, resulting in an increase in PDE4C mRNA stability, which contributes to the aforementioned malignant phenotypes. Consistently, the knockdown of PDE4C or ELAVL1 inhibited LNM of PTC cells, PTC growth, and Ki-67 expression in vivo. In summary, ELAVL1 promotes LNM in PTC by stabilising PDE4C. Our study elucidates the molecular mechanisms driving PTC metastasis, offering new therapeutic avenues for PTC treatment.