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Wilms' tumor 1-associating protein (WTAP) is ubiquitously expressed in many tissues and plays an important role in physiological processes and tumor development. Here, we investigated the specific biological role and underlying mechanism of WTAP in melanoma. We determined the expression of WTAP and its correlation with clinicopathological features in paraffin-embedded tissues. We investigated the effects of WTAP on melanoma cells via a CCK-8 assay, a colony formation assay, an EdU assay, a Transwell assay, and subcutaneous xenograft experiments. We then applied RNA sequencing to further screen candidate targets, and NT5E was selected as the downstream gene of WTAP. Finally, a series of rescue assays, together with nucleotidase assays and ELISA, were adopted to confirm the function of NT5E in melanoma progression. We demonstrated that WTAP expression was downregulated in melanoma, which was associated with a poor prognosis, and that WTAP expression served as an independent predictor of melanoma survival. Functionally, WTAP hindered the proliferation, growth, migration, and invasion of melanoma cells. Furthermore, NT5E was identified as the downstream effector of WTAP and was subsequently found to rescue the increased proliferation, migration, and invasion of melanoma cells induced by WTAP deficiency. Moreover, knockdown of WTAP increased the expression of NT5E, MMP2, and N-cadherin, and simultaneous transfection with siNT5E reversed the increased expression of MMP2 and N-cadherin. Moreover, increased NT5E expression caused by forced WTAP inhibition in melanoma promoted the hydrolysis of AMP to produce more adenosine and further abrogated the secretion of IFN-γ by PBMCs. We found that WTAP expression is significantly downregulated and restrains the progression of melanoma via the downstream effects of NT5E on immunosuppression and molecular adhesion. This study revealed that WTAP plays a crucial inhibitory role in melanoma oncogenesis and highlighted WTAP as a potential novel diagnosis and therapeutic target for melanoma.

Previous studies have shown that Ras-Related Nuclear Protein (RAN), a member of the RAS superfamily, is a small GTPase and an important oncogene in several cancers. However, its role in multiple myeloma (MM) and its potential contribution to drug resistance remain undetermined. Bioinformatics was employed to analyze differentially expressed genes in MM samples. RT-qPCR and western blotting were utilized for protein transcription and expression analysis. The CCK-8 assay was adopted to evaluate cell proliferation, and in vivo animal experiments were conducted to validate the results. The findings reveal that RAN represents one of the most significantly aberrant genes in MM, with its expression significantly elevated in both MM tissues and cells. Genetic manipulation experiments demonstrated that RAN promotes MM cell proliferation by activating the Wnt/PCP pathway. Concurrently, RAN governs the response of MM cells to the anti-cancer drug bortezomib (BTZ). Knockdown of RAN leads to increased sensitivity to BTZ. Mechanistic studies indicate that RAN influences drug response by regulating the activation of the JNK/c-Jun axis, thereby affecting the therapeutic response of MM cells. In summary, the upregulated expression of RAN in MM leads to BTZ resistance via activation of the Wnt/PCP pathway, potentially serving as a novel therapeutic target for MM.

Colorectal cancer (CRC) is a malignant tumor originating in the mucosal epithelium of the colon or rectum and is among the most common cancers of the digestive system. Now it is the fourth deadliest cancer in the world. Stimulator of Interferon Genes (STING) is a dimeric transmembrane protein on the endoplasmic reticulum membrane that induces the secretion of type I interferons and pro-inflammatory cytokines and is triggered by the cell membrane DNA of pathogens and hosts. It is widely expressed in immune cells (such as dendritic cells, macrophages) and some tumor cells, and has been shown to play a crucial role in the development of several tumors. However, issues such as the expression of STING in CRC and patient prognosis remain to be further elucidated. We investigated the expression of STING (in CRC tumor cells) and immune markers (CD3, CD4, CD8, CD56, CD163) in 86 CRC patients by tissue microarray using multicolor immunohistochemistry. Subsequently, the effect of STING on the tumor immune microenvironment was further explored. Finally, we analyzed the clinical significance of STING in CRC patients. We found elevated STING expression in tumor cells from CRC patients, which correlated with overall patient survival. High STING levels were associated with suppression of lymph node metastasis and reduction of CD163 tumor-associated macrophages. In contrast, upregulation of STING promoted infiltration of CD3+ T lymphocytes and CD8 lymphocyte subtype in the tumor microenvironment. Our study demonstrated that changes in STING expression in cancer cells in the tumor immune microenvironment have clinical significance and regulatory roles. STING-related functional mechanisms can be considered as therapeutic targets for CRC, which provides a theoretical basis for the subsequent clinical application of STING agonists.

The aim of our research was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for the liver in all patients diagnosed with either primary liver tumor or metastases from other primary malignancies since its initial application at a single institution. A retrospective analysis of the prospective designed registry included 105 patients with 133 liver metastases or primary tumors treated with SBRT from the introduction of the technique in March 2018 until November 2023. The main objectives of the study were to evaluate treatment toxicity, disease control, and survival rates. At a median follow-up of 24 months, a complete response to treatment was achieved in 86.7% of patients. During irradiation, only one patient experienced grade 3 abdominal discomfort, while the other 34.3% of patients experienced only mild acute adverse events (AEs), the majority of which were nausea. After completion of SBRT, 36.2% of patients reported AEs, but only grade 1 and 2 toxicity was observed. The one-, two-, and five-year LC rates were 89.2%, 84.9%, and 84.9%, respectively. DFS rates were 54.7%, 42.9%, and 25.8%; DSS rates were 94.9%, 81.1%, and 46.8%; and OS rates at one, two, and five years were 93.1%, 79.6%, and 43.2%, respectively. In the multivariate analysis, only the number of lesions presented independent prognostic value. In conclusion, SBRT offers effective disease control and survival rates with minimal toxicity, side by side with surgical options as a curative treatment for liver tumors.

The application of adjuvant therapy following neoadjuvant treatment and subsequent esophagectomy remains a subject of debate due to the limited availability of comprehensive studies. This study aims to evaluate the role of adjuvant therapy in patients with esophageal adenocarcinoma (EAC) who have undergone neoadjuvant therapy and esophagectomy, thereby offering evidence-based guidance for clinical decision-making. Patients diagnosed with EAC and treated with neoadjuvant therapy followed by surgical intervention were enrolled in our study. The data for patients in the training cohort were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To validate the findings, new patient cohorts were utilized. A total of 3,445 patients with EAC were identified from the SEER database based on the established eligibility criteria. The analysis revealed no significant differences between the adjuvant therapy group and the non-adjuvant therapy group in terms of 5-year overall survival, with rates of 35.7% and 37.2%, respectively (p=0.920), nor in 5-year cancer-specific survival, with rates of 39.5% and 43.2%, respectively (p=0.520). Additionally, 130 patients were identified from the Affiliated Jinling Hospital of Nanjing University's Medical School. In this cohort, findings indicated that patients receiving adjuvant therapy demonstrated improved overall survival compared to those not receiving such therapy (p=0.031). Leveraging the SEER database, our study demonstrated that adjuvant therapy did not confer a survival advantage for patients with EAC following neoadjuvant therapy and surgery. In contrast, data analysis from the Affiliated Jinling Hospital, Medical School of Nanjing University in China, indicated that EAC patients might indeed benefit from adjuvant therapy after undergoing neoadjuvant treatment and esophagectomy.

Allogeneic stem cell transplantation (alloSCT) remains the established main treatment option with curative potential for many hematologic malignancies. We conducted a retrospective analysis of 104 adult patients who underwent alloSCT between March 2013 and November 2023. Kaplan-Meier survival analysis, the chi-square test, and Cox regression models were used to identify risk factors and outcomes. The median follow-up of the cohort was 19 (0.3-128.1) months. The median age of the recipients was 49 (19-65) years, and 57 (54.8%) recipients were males. Ninety (86.5%) patients had a matched sibling, and 14 (13.5%) had a haploidentical donor. According to the multivariable analysis, a body mass index (BMI) ≥30 kg/m2 (p=0.02) and status without chronic graft-versus-host disease (cGVHD) (p=0.04) were significantly associated with worse overall survival (OS). A BMI ≥30 kg/m2 was also predictive of worse relapse-free survival (p=0.01). The cumulative incidence rates of nonrelapse mortality (NRM) and relapse mortality (RM) at 1 year were 8.5% (95% CI: 4.3-16.5%) and 26.7% (95% CI: 19.1-37.4%), respectively. Patients without cGVHD had significantly higher RM than patients with cGVHD (p<0.001), whereas patients with cGVHD had significantly higher NRM (p=0.01). Patients with a BMI ≥30 kg/m2 had significantly more posttransplant fatal events (p<0.001). Our analysis revealed that a BMI ≥30 kg/m2 and a status without cGVHD were significantly associated with worse OS. NRM was higher in patients with cGVHD, whereas patients without cGVHD died mostly from relapses.

CCL18, originating from M2-polarized tumor-associated macrophages (M2-TAMs) is recognized for its vital role in endometrial cancer (EC) development. Nonetheless, its precise mechanisms remain largely undefined. The primary objective of this research was to elucidate the underlying mechanism of M2-TAM-isolated CCL18 in EC progression. TWIST1 and HMGA1 expressions were assessed in EC tissues and cells by qRT-PCR or western blotting. M2 macrophages were differentiated from human monocyte THP-1 cells, and characterized via flow cytometry and western blotting. CCL18 levels were evaluated using western blotting and ELISA assay. CCK8, Transwell, and wound healing assays were employed to assess EC cell vitality, invasion, and migration, respectively, while western blotting was utilized to measure related protein markers. The binding relationship between TWIST1 and HMGA1 was validated via ChIP and dual-luciferase reporter assays. TWIST1 and HMGA1 were increased in EC tissues and cells. After being treated with M2-TAM-isolated CCL18, EC cell vitality, migration, and invasion were enhanced. Additionally, CCL18 derived from M2-TAM upregulated TWIST1 levels in EC cells. Further mechanistic analyses unveiled that TWIST could positively regulate HMGA1 in EC cells. Notably, HMGA1 knockdown restrained the malignancy of EC cells, which was reversed by TWIST1 overexpression. M2-TAM-isolated CCL18 facilitated EC progression by activating the TWIST1/HMGA1 axis. These observations might offer new directions for developing targeted curative interventions for EC.

Gliomas are primary intracranial tumors that cause considerable morbidity and mortality. The effect of interleukin 4-induced gene-1 (IL4I1) on the progression of various diseases has been demonstrated to be significant. However, the specific molecular mechanisms of how IL4I1 contributes to the progression and the epithelial-mesenchymal transition (EMT) process of glioma remain inadequately elucidated. IL4I1 expression in glioma was assessed using public datasets and immunohistochemistry. In in vitro experiments, IL4I1 expression was quantified through real-time quantitative PCR and western blotting. The effects of IL4I1 knockdown on the malignant phenotypes of glioma cells were investigated through in vitro studies. The evaluation of biomarkers associated with EMT and the Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway was conducted using western blotting and immunofluorescence assays after IL4I1 knockdown. A xenograft tumor model was established to validate the influence of IL4I1 knockdown in glioma progression. The results revealed that high expression of IL4I1 is linked to an unfavorable prognosis in human gliomas. IL4I1 knockdown effectively impeded the malignant phenotypes of glioma cells. IL4I1 knockdown induced EMT reversal, characterized by alterations in the expression levels and localization of EMT-related biomarkers. This reversal is partially mediated through the JAK2/STAT3 signaling pathway. The results of in vivo experiments confirmed that IL4I1 knockdown effectively suppressed glioma growth. Our research demonstrates that IL4I1 knockdown reverses the EMT process via JAK2/STAT3 signaling pathway and suppresses the malignant phenotypes of glioma, thereby highlighting its potential as both a prognostic marker and therapeutic target for glioma.

Triptonide, an active ingredient of Tripterygium wilfordii Hook. F., has been found to have anticancer effects on various cancers; however, its effect on oral squamous cell carcinoma (OSCC) has not yet been studied. This study aims to reveal the effect and mechanism of triptonide on OSCC. The inhibitory effect of triptonide on OSCC progression was ascertained by CCK-8 assay, EdU incorporation assay, wound healing assay, Transwell assay, and xenograft tumor model, while western blotting, qRT-PCR, and immunohistochemistry revealed that triptonide could inhibit c-Myc expression in OSCC. RNA-seq was conducted to explore the mechanism by which triptonide inhibited the progression of OSCC, and thyroid hormone receptor interactor 13 (TRIP13) was identified as a key differentially expressed gene. TRIP13-knockdown OSCC cells constructed with siRNA showed weaker progression ability in CCK-8 assay, EdU incorporation assay, wound healing assay, and Transwell assay. Finally, TRIP13-overexpressing OSCC cells constructed through plasmid were used in rescue experiments, which demonstrated that TRIP13 was located upstream of c-Myc and the overexpression of TRIP13 could partially restore the decreased c-Myc expression caused by triptonide treatment. Collectively, this study demonstrated that triptonide might reduce the expression of c-Myc by suppressing TRIP13 expression, thereby inhibiting the progression of OSCC. These findings have revealed a partial mechanism by which triptonide acts on OSCC and suggested its potential application value in OSCC treatment.

Kelch-like family member 7 (KLHL7) is associated with cancer development and occurrence, but its role and mechanism in the malignant progression of gliomas remain poorly understood. This study aimed to investigate the regulatory effects and mechanisms of KLHL7 on cell cycle and glutamine metabolism in glioma. Glioma cell lines A172 and U87 and a xenograft mouse model were used to analyze the function of KLHL7 in vitro and in vivo, respectively. Gene expression levels and protein amounts were assessed by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively. Cell viability was assessed using the CCK-8 assay, and the cell cycle was analyzed via flow cytometry. The glutamine content was measured using a biochemical assay. The level of KLHL7 was upregulated in patients with glioma. KLHL7 knockdown reduced cell viability, inhibited cell cycle progression, and decreased the glutamine content in A172 cells. KLHL7 silencing inhibited tumor growth in vivo. Furthermore, KLHL7 overexpression enhanced cell viability, cell cycle progression, and glutamine metabolism and activated the β-catenin signaling pathway in U87 cells. These findings indicate that KLHL7 promotes the malignant progression of glioma via the β-catenin signaling pathway and may serve as a biomolecule for the clinical prediction and treatment of the disease.