Neoplasma最新文献

F-box and WD repeat domain containing 7 (FBXW7) is an aboriginal and high-frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis, and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the mechanism of FBXW7. FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR array revealed that FBXW7 overexpression leads to a significant change of gene expressions associated with angiogenesis, cell senescence, and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage, and repair in ESCC.

Metabolic rewiring of tumor cells leads to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment of solid tumors has been reported to support tumor-infiltrating regulatory T (Treg) cells. Therefore, agents that modify the lactate metabolism of Treg cells have therapeutic potential. Monocarboxylate transporter 1 (MCT1), which Treg cells predominantly express, plays an essential role in the metabolism of tumor-infiltrating Treg cells. In this study, we show that miR-124 directly targets MCT1 and reduces lactate uptake, eventually impairing the immune-suppressive capacity of Treg cells. Particularly, exosomal miR-124 derived from bone marrow mesenchymal stromal cells (BM-MSCs) slows tumor growth and increases response to PD-1 blockade therapy. These data indicate a potential treatment strategy for improving immune checkpoint blockade therapy using miR-124-carried BM-MSCs-derived exosomes.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. A number of studies have confirmed that coiled-coil domain-containing protein 86 (CCDC86) plays an important role in the pathogenesis of lymphoma but the role of CCDC86 in NPC has not yet been reported. Here, in vivo and in vitro experiments were conducted to explore whether CCDC86 plays a role in the pathogenesis of NPC and to identify the specific mechanism. We found that CCDC86 was highly expressed in NPC tissues and cells, and the expression level of CCDC86 was correlated with the prognosis of patients with advanced NPC. CCDC86 promoted the proliferation, invasion, and migration of NPC cells in vivo and in vitro by promoting the EMT process and upregulating the expression of MMPs. Then, we confirmed that EGFR is a downstream target gene of CCDC86 and that CCDC86 can promote the proliferation, invasion, and migration of NPC cells by upregulating the expression of EGFR and activating downstream PI3K/Akt. Furthermore, we confirmed that CCDC86 did not directly bind to EGFR but positively regulated EGFR by binding to NPM1. CCDC86 is expected to be used as a novel biomarker and therapeutic target for predicting the prognosis of NPC.

Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions.

Currently, less than 200 cases of SMARCB1-deficient sinus cancer (SDSC) have been documented. Little information is available about the best treatment options or prognosis for SDSC. From September 2016 to November 2022, the medical records of 22 people with SDSC were evaluated retrospectively. Patient demographics, staging, pathology findings, treatment details, recurrence, metastasis, and survival outcomes were all investigated by the researchers. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort were 89.8%, 84.2%, and 45.1%, respectively, as were the 1-, 2-, and 3-year progression-free survival (PFS) rates of 81.8%, 63.8%, and 31.9%. After induction chemotherapy, 66.7% (10/15) of patients exhibited decreased tumor volume. Patients who accepted chemoradiotherapy had a better 2-year OS (100% vs. 72.7%, p=0.048) than those who accepted surgery as a preference. However, there is no difference in 2-year PFS between the two groups (53.0% vs. 75.8%, p=0.59). Patients with progressed or stable disease after induction chemotherapy had a higher risk of developing local recurrence (p=0.007); they also showed poor 2-year PFS (40.0% vs. 82.1%, p=0.019). SDSC had a poor 3-year OS, with a PFS of less than 50%. For locally advanced SDSC, chemoradiotherapy might be managed before surgery, especially in patients who benefit from induction chemotherapy.

Pancreatic cancer is one of the most lethal tumors due to its rapid proliferation and aggressiveness. RAD51AP1 is a protein-coding gene with critical functions in many cancers but few studies have assessed RAD51AP1 in pancreatic cancer. Bioinformatics methods and cell function experiments were performed to reveal the functions of RAD51AP1 in vitro. Gene Expression Profiling Interactive Analysis (GEPIA) was used to explore key proteins and their relationships with RAD51AP1 in the PI3K/AKT/NF-κB signaling pathways. Western blotting (WB) was conducted to detect the expression of key proteins after the downregulation of RAD51AP1. Co-Immunoprecipitation (Co-IP) was applied to confirm the binding of RAD51AP1 and PI3K. In addition, the lentivirus was used to construct subcutaneous tumors in nude mice to verify the function of RAD51AP1 in vivo. The Kaplan-Meier curves illustrated that elevated expression levels of RAD51AP1 were significantly correlated with reduced overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in pancreatic cancer patients. The results of WB showed that several key proteins in the PI3K/AKT/NF-κB signaling pathway (including PI3K, AKT, IKK1, IKK2, P65, P50, C-FLIP, and XIAP) exhibited a significant knockdown upon reducing the expression of RAD51AP1. Co-IP suggested that RAD51AP1 could directly bind to PI3K. In vitro, CCK-8, wound healing, and Transwell assays revealed that high RAD51AP1 expression was significantly correlated with increased cell proliferation, migration, and invasion. In vivo, mouse tumor formation experiments showed that RAD51AP1 inhibition significantly inhibited tumor growth. RAD51AP1 plays an important role in fostering cellular proliferation, invasion, metastasis, and tumor enlargement via the PI3K/AKT/NF-κB signaling pathway.

Cervical cancer (CC) is a common cancer in women and a serious threat to women's lives. TRIM11 has been confirmed as a carcinogen in multiple cancers. Here, we will excavate the detailed mechanism of TRIM11 in CC. CC cell lines and nude mice were experimental subjects in this study. The abundance of genes and proteins was detected using qRT-PCR, western blot, and IHC. Cell proliferation, migration, and invasion were determined by CCK-8 assay, wound healing assay, and Transwell, respectively. The interactions among METTL14, TRIM11, and PHLPP1 were confirmed using RIP and co-IP, respectively. The stability of TRIM11 mRNA was examined by qRT-PCR with actinomycin D treatment. The m6A level of TRIM11 was detected by MeRIP assay. Results showed that TRIM11 levels were elevated in CC cells. TRIM11 depletion attenuated the proliferation, migration, and invasion of Hela and SiHa cells. Additionally, TRIM11 was modified with m6A, which was mediated by METTL14, and the stability of TRIM11 mRNA was enhanced by IGF2BP1 depending on the level of m6A modification. TRIM11 ubiquitinated PHLPP1 and led to reduced PHLPP1 expression at the protein level. PHLPP1 could further result in the dephosphorylation of AKT and inhibit AKT signaling. PHLPP1 knockdown neutralized TRIM11 silencing-mediated repression of malignant phenotypes of CC cells. TRIM11 mediated by the METTL14-IGF2BP1 axis promotes the AKT pathway to accelerate CC progression by mediating the ubiquitination of PHLPP, which might provide novel therapeutic targets for CC treatment.

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality. It is well-accepted that dysregulated lncRNAs are closely related to the development of CRC. In this study, the function and mechanism of RNASEH1-AS1 in CRC were investigated. RT-qPCR and western blot detected the expression of targeted genes in tissues and cells. CCK-8, clone formation, wound healing assay, and Transwell were applied to evaluate CRC cell malignant behaviors. ChIP, RIP, and RNA pull-down validated interactions among RNASEH1-AS1, H3K27ac, CBP, BUD13, and ANXA2. Nucleoplasmic separation and FISH assay determined the location of RNASEH1-AS1 in CRC cells. IHC assay was used to detect Ki-67 expression in tumor tissues from mice. RNASEH1-AS1 was highly expressed in CRC tumor tissues and cells. RNASEH1-AS1 silencing effectively suppressed the viability, proliferation, migration, and invasion of CRC cells. In addition, CBP-mediated H3K27ac increased RNASEH1-AS1 expression in CRC cells and RNASEH1-AS1 could elevate ANXA2 expression through recruiting BUD13. Furthermore, RNASEH1-AS1 silencing inhibited malignant phenotypes of CRC cells and tumor growth in mice through decreasing ANXA2 expression and inactivating the Wnt/β-catenin pathway. Our results revealed that RNASEH1-AS1 induced by CBP-mediated H3K27ac activated Wnt/β-catenin pathway to promote CRC progression through recruiting BUD13 to stabilize ANXA2 mRNA, which provides substantial evidence of RNASEH1-AS1 in CRC. Targeting RNASEH1-AS1 might alleviate CRC progression.

Radiotherapy and chemotherapy have improved the 5-year survival rate of nasopharyngeal carcinoma (NPC) patients, but the side effects generally lead to unsatisfactory clinical efficacy. It's imperative to explore the pathogenesis of NPC to find better diagnostic and therapeutic methods. Small nucleolar RNA host genes (SNHGs) are special lncRNAs, which can be further spliced to produce small nucleolar RNAs (snoRNAs). SNHG1 has been found to be associated with various cancers. However, only a few studies reported the relationship between SNHG1 and NPC. This study first analyzed the diagnostic performance and related signaling pathways of SNHG1 in NPC through bioinformatics. The expression of SNHG1 was verified by RT-qPCR, and the expression of the signaling pathway was detected using immunohistochemistry. Bioinformatics analysis results showed that SNHG1 was significantly overexpressed in head and neck squamous cell carcinoma (HNSC) and NPC tissues. RT-qPCR detection confirmed the significant overexpression of SNHG1 in NPC tissues. Enrichment analysis showed that SNHG1 may act on NPC through the PI3K-AKT signaling pathway. Immunohistochemistry experiment revealed PI3K-AKT signaling pathway proteins (PI3K AKT and EGFR) positively expressed and CASP3 weakly positively expressed in NPC tissues. Therefore, we concluded that SNHG1 is a prospective biomarker and may act on NPC through the PI3K-AKT signaling pathway.

Minichromosome maintenance complex component 2 (MCM2) is a member of the MCM family and is involved in various cancers. However, the role of MCM2 in endometrial cancer (EC) remains unclear. In this study, we aim to determine the biological function of MCM2 in EC cells and identify the potential underlying mechanisms. MCM2 expression and prognostic significance were analyzed in TCGA-UCEC datasets. Combining bioinformatics analyses and experiments, stemness-related molecules and phenotypes were examined to evaluate the impact of MCM2 on stemness in EC cells. The major findings of these analyses are as follows: 1) MCM2 is expressed at higher levels in EC tissues than in normal endometrial tissues. High expression of MCM2 is related to the characteristics of poorly differentiated EC. High MCM2 expression is correlated with poor overall survival in EC patients; 2) MCM2 knockdown was found to decrease sphere formation ability, downregulate the expression of stemness-related molecules, and reduce the proportion of CD133+ cells, while MCM2 overexpression elicited the opposite effect in EC cells; 3) MCM2-mediated stemness features are dependent on the activation of Akt/β-catenin signaling pathways; and 4) MCM2 knockdown increases cisplatin sensitivity in EC cells. MCM2 regulates stemness by regulating the Akt/β-catenin signaling pathway in EC cells.