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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.

Radiotherapy is widely used as the first-line treatment for nasopharyngeal carcinoma (NPC). However, the resistance of some patients to treatment lowers its clinical effectiveness. Compared to typical epithelial cells, NPC markedly lowers the Ras-association domain family 1A (RASSF1A) protein expression. RASSF1A overexpression sensitizes NPC cells to radiotherapy. Mechanistically, RASSF1A promotes the expression of Forkhead box O3a (FoxO3a) in the nucleus and inhibits the Nuclear factor E2-related factor 2 (Nrf2) signaling pathway via binding to the Kelch-like ECH-associated protein 1 (Keap1) promoter. Through elevating intracellular ROS levels, RASSF1A overexpression inhibits the expression of thioredoxin reductase 1 (TXNRD1), a crucial Nrf2 target gene, and increases NPC sensitivity to radiation. Immunohistochemical staining of NPC tissue sections revealed that the expression of RASSF1A is negatively correlated with that of TXNRD1. The traditional Chinese medicine component andrographolide (AGP), which induces RASSF1A expression, increased the sensitivity of NPC cells to radiotherapy in vitro and in vivo. Our findings implied that RASSF1A increases the sensitivity of NPC to radiation by increasing FoxO3a expression in the nucleus, inhibiting the Nrf2/TXNRD1 signaling pathway, and elevating intracellular ROS levels. AGP targets RASSF1A and may be a promising adjuvant sensitizer for enhancing radiosensitivity in NPC.

High cholesterol is an important factor inducing colorectal cancer (CRC). The study aims to determine the key genes and regulatory mechanism associated with tumor-infiltrating T cells underlying cholesterol-induced CRC. Gene expression data and clinical data from CRCS in The Cancer Genome Atlas (TCGA) were selected for differential expression and survival analysis. A total of 5,815 DEGs and 21 cholesterol-associated KEGG pathways were identified. Subsequently, 128 CRCs and 127 patients without obvious intestinal lesions were recruited to analyze the relationship between GPX3 expression, cholesterol levels, and pathologic condition. The results showed that the expression of cholesterol-related gene GPX3 was negatively associated with cholesterol level, but positively correlated with Ki-67 proliferation index in CRC. The expression of GPX3 was higher in CRC patients who were in poorly differentiated and advanced stage. In addition, a mice model of high-cholesterol diet intervention was constructed to detect the levels of cholesterol and GPX3 in the peripheral blood of mice, and it was found that the expression level of GPX3 in high-cholesterol mice was lower than that in normal diet mice. CD8+ T cells were isolated from the spleen of mice and the T cell surface receptors were detected. It was found that the expression of CD69 in CD8+ T cells of mice interfered with the high-cholesterol diet, while the expression of PD1, TIM-3, and CTLA-4 was increased. CD8+ T cells were co-cultured with MC38 cells to detect the proliferation rate of CRC cells. The results showed that the tumor cell proliferation ratio in the high cholesterol group was higher than that in the control group. Furthermore, GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were screened, and a T cell immune-related ceRNA network was constructed. In total, 53 GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were identified. A PPI network that contained 45 nodes and 85 interaction pairs was constructed. The ceRNA network, including 39 miRNA-target and 43 lncRNA-miRNA regulatory pairs, was constructed. In conclusion, GPX3 is a potential target for cholesterol regulation of T cell immunity in CRC.