To study the effect of congenital dyskeratosis 1 (DKC1) on neuroblastoma and its regulation mechanism. The expression of DKC1 in neuroblastoma was analyzed by TCGA database and molecular assay. NB cells were transfected with siDKC1 to observe the effects of DKC1 on proliferation, cloning, metastasis, and invasion, and apoptosis and apoptosis-related proteins. The tumor-bearing mouse model was constructed, shDKC1 was transfected to observe the tumor growth and tumor tissue changes, and the expression of DKC1 and Ki-67 was detected. Screening and identification of miRNA326-5p targeting DKC1. NB cells were treated with miRNA326-5p mimic or inhibitors to detect the expression of DKC1. NB cells were transfected with miRNA326-5p and DKC1 mimics to detect cell proliferation, apoptosis, and apoptotic protein expression. DKC1 was highly expressed in NB cells and tissues. The activity, proliferation, invasion, and migration of NB cells were significantly decreased by DKC1 gene knockout, while apoptosis was significantly increased. The expression level of B-cell lymphoma-2 in shDKC1 group was significantly lower than that of the control group, while the expression level of BAK, BAX, and caspase-3 was significantly higher than that of the control group. The results of experiments on tumor-bearing mice were consistent with the above results. The results of miRNA assay showed that miRNA326-5p could bind DKC1 mRNA to inhibit the protein expression, thereby inhibiting the proliferation of NB cells, promoting their apoptosis, and regulating the expression of apoptotic proteins. miRNA326-5p targeting DKC1 mRNA regulates apoptosis-related proteins to inhibit neuroblastoma proliferation and promote the apoptotic process.

Background. NKG2A (KLRC1) belongs to the NKG2 family, which has been shown to affect the activity of natural killer (NK) cells and CD8T cells. However, a comprehensive biological analysis and exploration of NKG2A in different cancers is lacking and this needs to be further investigated. Methods. A comprehensive pan‐cancer analysis of NKG2A was performed based on multiple databases. The Cancer Genome Atlas (TCGA) and Genotype–Tissue Expression (GTEx) databases were used to analyze the expression profile of NKG2A in pan‐cancer. The relevance of NKG2A to the prognosis of different cancers was assessed using Kaplan–Meier survival analysis. In addition, we explored the correlation between NKG2A expression and gene mutations, pathological staging, tumor‐infiltrating immune cells (TIICs), DNA methyltransferase (DNMT) genes, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and immune checkpoints (ICPs). Finally, the expression levels of NKG2A in several cancer cell lines were verified by qRT‐PCR. Results. Pan‐cancer comprehensive analysis showed that NKG2A expression levels were significantly different between multiple cancers and corresponding normal tissues. The differential expression of NKG2A was related to the prognosis and pathological staging of patients with multiple cancers, and was closely related to the excessive infiltration of immune cells and the regulation of ICP genes in the tumor microenvironment (TME). In addition, TMB, MSI, MMR, and DNMT genes in many cancer types are also affected by NKG2A expression. Gene set enrichment analysis (GSEA) showed that NKG2A was associated with multiple immune‐related functions and pathways in malignant tumors. qRT‐PCR results showed that NKG2A was underexpressed in liver, gastric, and colon cancer cell lines compared to normal cells, which was consistent with bioinformatics analysis. Conclusion. The present study suggests that NKG2A may be a potential predictive biomarker for cancer immune response and prognosis.

Gliosarcoma (GSM), a histologic variant of glioblastoma (GBM), carries a poor prognosis with less than one year of median survival. Though GSM is similar with GBM in most clinical and pathological symptoms, GBM has unique molecular and histological features. However, as the rarity of GSM samples, the genetic information of this tumor is still lacking. Here, we take a comprehensive analysis of DNA copy number variations (CNV) in GBM and GSM. Whole genome sequencing was performed on 21 cases of GBM and 15 cases of GSM. CNVKIT is used for CNV calling. Our data showed that chromosomes 7, 8, 9, and 10 were the regions where CNV frequently happened in both GBM and GSM. There was a distinct CNV signal in chromosome 2 especially in GSM. The pathway enrichment of genes with CNV was suggested that the GBM and GSM shared the similar mechanism of tumor development. However, the CNV of some screened genes displayed a disparate form between GBM and GSM, such as AMP, BEND2, HDAC6, FOXP3, ZBTB33, TFE3, and VEGFD. It meant that GSM was a distinct subgroup possessing typical biomarkers. The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

Currently, the Thinprep cytologic test (TCT) is the most popular cervical cancer cytology test technique. It can detect precancerous conditions and microbial infections. However, this technique entirely relies on manual operation and doctors' naked eye observation, resulting in a heavy workload and low accuracy rate. Recently, automatic pathological diagnosis has been developed to solve this problem. Cervical cell classification is a key technology in the intelligent cervical cancer diagnosis system. Training a deep neural network-based classification model requires a large amount of data. However, cervical cell labeling requires specialized physicians and the cost of labeling is high, resulting in a lack of sufficient labeling data in this field. To address this problem, we propose a method to ensure high accuracy in cervical cell classification with a small amount of labeled data by introducing manual features and a voting mechanism to achieve data expansion in semi-supervised learning. The method consists of three main steps, using a clarity function to filter out high-quality cervical cell images, annotating a small amount of them, and balancing the training data using a voting mechanism. With a small amount of labeled data, the accuracy of the proposed method in this paper can reach to 91.94%.

Statistical reports on non-Hodgkin's lymphoma (NHL) of the head and neck combining clinical medicine with pathology are rare. To provide a basis for prognosis prediction and individualized treatment, we will investigate the clinicopathologic characteristics and prognosis of lymphoma in the head and neck region. Four hundred sixty-one patients with NHL in the head and neck region diagnosed through histological biopsy were retrospectively analyzed. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed in all cases to evaluate the genetic status and protein expression levels. Patients were followed up by telephone. The prevalence rate of primary extranodal NHL (PENHL) in the head and neck region was 44.62% (166/372). The incidence of extranodal lymphoma accounted for 36.66% (169/461) of all head and neck lymphomas. Among the cases of PENHL of the head and neck, diffuse large B-cell lymphoma (DLBCL) (60/76, 78.95%) and extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (21/24, 87.5%) were the most common subtypes originating from B-cell lymphoma (BCL) and T-cell lymphoma (TCL), respectively. The most common sites of nodal and extranodal onset were neck lymph nodes and the gastrointestinal tract, respectively. The most common and primary locations of BCL and TCL were the tonsils and nasal cavity, respectively. The 3-year survival rates of PENHL, ENKTCL, and DLBCL of the head and neck were 42%, 28.57%, and 41.67%, respectively, and the 5-year survival rates were 24%, 19.05%, and 20%, respectively. Survival analysis showed that male sex was a risk factor (HR = 5.421; 95% CI, 1.164-25.267; p < 0.05) and that comprehensive treatment was a protective factor (HR = 0.117; 95% CI, 0.025-0.545; p < 0.05) against extranodal DLBCL in the head and neck region. Bone marrow involvement was a risk factor for PENHL of the head and neck (HR = 5.072; 95% CI, 1.17-21.991; p < 0.05). The purpose of this review is to show that PENHL of the head and neck with high incidence deserves more attention, and a model of multidisciplinary diagnosis and treatment should be adopted.

Overexpressed survivin is associated with worse survival of several types of human tumors. In this study, the antitumor activity of shikonin in non-small-cell lung cancer (NSCLC) by regulating survivin pathway was investigated. Results showed that shikonin inhibited the NSCLC H1299 cell proliferation in a dose-dependent manner. Moreover, shikonin fits well with survivin by molecular docking. Shikonin also inhibited the mRNA expression and protein level of survivin in H1299 cells. Shikonin arrested H1299 cell cycle at the G0/G1 phase by regulating CDK/cyclin family members. In addition, shikonin regulated the expression of X-linked inhibitor of apoptosis- (XIAP-) mediated caspases 3 and 9, thus leading to the damage of mitochondrial membrane potential and induction of H1299 cell apoptosis. Overall, shikonin inhibited H1299 cell growth by inducing apoptosis and blocking the cell cycle. The underlying mechanism involves targeting survivin, which subsequently regulates the protein expression of XIAP/caspase 3/9, CDK2/4, and cyclin E/D1. Thus, shikonin, a survivin inhibitor, is a promising therapeutic strategy in NSCLC treatment.

Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer worldwide. Strong connections have been revealed between immune cells and the pathogenesis of HNSCC. Important differences regarding the levels of immune cell subpopulations in both peripheral circulation and tumor microenvironment were emphasized, with some of them having prognostic significance. In our study, we performed an analysis of immune changes in the tumor tissue and the peripheral blood of untreated HNSCC patients, investigating the proportions of different immune cell populations in these two compartments. The local infiltrating lymphocytes were mainly cytotoxic T cells (CD8+). We have also revealed an increased level of B lymphocytes (CD19+) in the tumor microenvironment. In peripheral blood, the most important lymphocyte subtype was represented by the helper T lymphocytes (CD4+). We also found an increased proportion of circulating NK cells (CD56+). Our results showed significant differences between all investigated lymphocyte subtypes in the peripheral blood and the tumor tissue of untreated HNSCC patients, suggesting that the local and systemic expressions of antitumor immune responses are different and that investigation of immune cell proportions in peripheral circulation has different cues that do not reflect the immune infiltrate pattern within the tumor microenvironment. Further studies are necessary to unveil the complex interplay involving local and systemic events in the immune system's fight against cancer.

Background Accumulating evidence shows that autophagy plays a vital role in tumor occurrence, development, and metastasis and even determines tumor prognosis. However, little is known about its role in papillary thyroid carcinoma (PTC) or the potentially oncogenic role of TFE3 in regulating the autophagy-lysosome system. Methods Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to examine the expression of TFE3, P62/SQSTM1, and LC3 in PTC and paracancerous tissues. TFE3, P62/SQSTM1, LC3, cathepsin L (CTSL), and cathepsin B (CTSB) were evaluated using Western blot analysis. After inducing TFE3 overexpression by plasmid or TFE3 downregulation by small interfering RNA (siRNA) transfection, MTT, wound healing, and cell migration and invasion assays were used to verify the effects on invasion, migration, and the levels of autophagy-lysosome system-related proteins such as P62/SQSTM1, LC3, CTSL, and CTSB. Results TFE3 was overexpressed in PTC tissues compared with paracancerous tissues. Analysis of the clinicopathological characteristics of PTC patients showed that high TFE3 expression was significantly correlated with lymph node metastasis. TFE3 overexpression in the PTC cell lines KTC-1 and BCPAP promoted proliferation, invasion, and migration, while TFE3 knockdown had the opposite effects. Furthermore, we identified a positive relationship among the expression levels of TFE3, P62/SQSTM1, LC3, CTSL, and CTSB. We found that silencing TFE3 inhibited the expression of P62/SQSTM1, LC3, CTSL, and CTSB in PTC cells. However, TFE3 overexpression had the opposite effects. Conclusions The present study provided evidence for the underlying mechanisms by which TFE3 induces autophagy-lysosome system activity in PTC.

Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.