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Extranodal extension in metastatic lymph nodes (LNs) is a poor prognostic factor in bladder cancer (BC). Furthermore, cancer invasion levels in sentinel LNs are associated with prognosis in melanoma. The present study aimed to evaluate the LN invasion level, defined as the extent of cancer invasion in anatomical and immunological LN substructures, and compare it with the pathological node (pN) stage of the tumor-node-metastasis staging system in BC. A total of 98 patients with BC who underwent radical cystectomy and pelvic lymphadenectomy were retrospectively assessed. The LN invasion level was classified as follows: Level 0, no cancer cell within the resected LNs; Level 1, cancer cells confined to intracapsular lymph vessels and subcapsular or transverse sinuses; Level 2, cancer cells infiltrating the cortex, paracortex or medulla; and Level 3, cancer cells infiltrating or beyond the LN capsule. The proportion of patients with Levels 0, 1, 2 and 3 was 70.4% (69/98), 8.2% (8/98), 14.3% (14/98) and 7.1% (7/98), respectively. Kaplan-Meier survival curves of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) with LN invasion levels better strati- fied outcome patient when using Levels 1-3 compared with pN1-3. In addition, LN invasion levels better predicted RFS, CSS and OS, in comparison with the pN stage (c-index of 0.672 vs. 0.646, 0.688 vs. 0.665, and 0.702 vs. 0.661, respectively). Finally, multivariate analysis revealed that the predictive accuracy of the model integrating pathological tumor (pT) stage and LN invasion levels in RFS, CSS and OS was greater than that of the conventional model that included pT and pN stage (c-index of 0.723 vs. 0.703, 0.710 vs. 0.694, and 0.725 vs. 0.692, respectively). In conclusion, the model with LN invasion levels accurately predicted the prognosis of patients with BC after radical cystectomy and pelvic lymphadenectomy. [ABSTRACT FROM AUTHOR]

Breast cancer typically arises from the terminal duct-lobular unit of the mammary gland and rarely from the ducts inside the nipple. The present paper reports a rare case of primary invasive ductal carcinoma of the papilla, which was a locally advanced triple-negative breast cancer that was treated with 6 cycles of neoadjuvant chemotherapy with a nab-paclitaxel, epirubicin and cyclophosphamide regimen. Surgical pathology confirmed that a pathological complete response was achieved and adjuvant radiotherapy was performed postoperatively. No recurrence or metastasis occurred as of April 2024. A review of previous similar cases revealed that primary invasive breast cancer of the nipple has several manifestations. Changes in the nipple should be treated cautiously and a pathological biopsy should be performed in a timely manner. Breast cancer occurring in the nipple can be treated with reference to the same type of common breast cancer, and neoadjuvant chemotherapy can also be performed first if neoadjuvant chemotherapy is indicated. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have a demonstrable treatment response in patients with resectable non-small cell lung cancer (NSCLC). However, immune-related adverse events and tumor progression in patients administered ICIs are of great concern. The present case study is of a 59-year-old male with NSCLC (squamous, stage IIIA) who received neoadjuvant immunotherapy combined with chemotherapy before surgery. The patient first developed hyperthyroidism and then hypothyroidism, indicating that ICI-related thyroid dysfunction had occurred. Furthermore, the patient suffered from tumor progression and could not undergo resection. The present case called attention to the prevention and management of irAEs, and the precaution that should be taken with regard to tumor progression. The case also suggested that the development of ICI-related thyroid dysfunction may not predict an improved response to ICI therapies, which needs further evidence to illustrate. [ABSTRACT FROM AUTHOR]

Cancer is a serious and potentially life-threatening disease, which, despite numerous advances over several decades, remains a challenge to treat that challenging to detect at an early stage or treat during the later stages. Long noncoding RNAs are >200 nucleotides long and do not possess protein-coding capacity, instead regulating cellular processes, such as proliferation, differentiation, maturation, apoptosis, metastasis, and sugar metabolism. Several studies have shown the role of lncRNAs and glucose metabolism in regulating several key glycolytic enzymes and the activity of multiple functional signaling pathways during tumor progression. Thus, it is possible to further learn about the effects of lncRNA and glycolytic metabolism on tumor diagnosis, treatment, and prognosis through a thorough investigation of the lncRNA expression profiles and glycolytic metabolism in tumors. This may provide a novel strategy for improving the management of several types of cancer. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the significance and molecular mechanisms of galectin-1 (LGALS1) in ovarian cancer (OC). Using the Gene Expression Omnibus database and The Cancer Genome Atlas database, the results of the present study demonstrated that LGALS1 mRNA expression was markedly increased in OC and associated with advanced tumor, lymphatic metastasis and residual lesions. In Kaplan-Meier analysis, patients who expressed LGALS1 highly had a poor prognosis. Furthermore, using The Cancer Genome Atlas database, differentially expressed genes that are potentially regulated by LGALS1 in OC were determined. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to build a biological network of upregulated differentially expressed genes. The results of the enrichment analysis revealed that the upregulated differentially expressed genes were primarily associated with 'ECM-receptor interaction', 'cell-matrix adhesion' and 'focal adhesion', which are closely associated with the metastasis of cancer cells. Subsequently, cell adhesion was selected for further analysis. The results demonstrated that LGALS1 was co-expressed with the candidate genes. Subsequently, the elevated expression levels of candidate genes were verified in OC tissues, and survival analysis indicated that high expression of candidate genes was associated with shortened overall survival of patients with OC. In the present study, OC samples were also collected to verify the high protein expression levels of LGALS1 and fibronectin 1. The results of the present study highlighted that LGALS1 may regulate cell adhesion and participate in the development of OC. Therefore, LGALS1 exhibits potential as a therapeutic target in OC. [ABSTRACT FROM AUTHOR]

Human health is endangered by the occurrence and progression of urological cancers, including renal cell carcinoma, prostate cancer and bladder cancer, which are usually associated with the activation of oncogenic factors and inhibition of cancer suppressors. The primary mechanism for protein breakdown in cells is the ubiquitin-proteasome system, whilst deubiquitinases contribute to the reversal of this process. However, both are important for protein homeostasis. Deubiquitination may also be involved in the control of the cell cycle, proliferation and apoptosis, and dysregulated deubiquitination is associated with the malignant transformation, invasion and metastasis of urologic malignancies. Therefore, a comprehensive summary of the mechanisms underlying deubiquitination in urological cancers may provide novel strategies and insights for diagnosis and treatment. The present review aimed to methodically clarify the role of deubiquitinating enzymes in urinary system cancers as well as their prospective application prospects for clinical treatment. [ABSTRACT FROM AUTHOR]

This document is a retraction notice from the journal Oncology Letters regarding a paper titled "miR-148a-3p suppresses epithelial ovarian cancer progression primarily by targeting c-Met." The retraction was prompted by a concerned reader who noticed that data in Figure 2C had already appeared in a different article by different authors. Since the contentious data had been submitted for publication prior to its submission to Oncology Letters, the editor decided to retract the paper. The authors were asked for an explanation but did not respond. The retraction notice apologizes for any inconvenience caused. [Extracted from the article]

Platelets (PLTs) facilitate tumor progression and the spread of metastasis. They also interact with cancer cells in various cancer types. Furthermore, PLTs form complexes with gastric cancer (GC) cells via direct contact and promote their malignant behaviors. The objective of the present study was to explore the molecular mechanisms driving these interactions and to evaluate the potential for preventing peritoneal dissemination by inhibiting PLT activation in GC cells. The present study examined the roles of PLT activation pathways in the increased malignancy of GC cells facilitated by PLT-cancer cells. Transforming growth factor-β receptor kinase inhibitor (TRKI), Src family kinase inhibitor (PP2) and Syk inhibitor (R406) were used to identify the molecules influencing these interactions. Their therapeutic effects were verified via cell experiments and validated using a mouse GC peritoneal dissemination model. Notably, only the PLT activation pathway-related inhibitors TRKI and PP2, but not R406, inhibited the PLT-enhanced migration and invasion of GC cells. In vivo analyses revealed that PLT-enhanced peritoneal dissemination was suppressed by PP2. Overall, the present study revealed the important role of the Srk family in the interactions between PLTs and GC cells, suggesting kinase inhibitors as promising therapeutic agents to mitigate the progression of peritoneal metastasis in patients with GC. [ABSTRACT FROM AUTHOR]

von Willebrand Factor (VWF) is well recognized for being dysregulated in various malignancies and has emerged as a potential biomarker for cancer detection. The present meta-analysis aimed to elucidate the association between plasma VWF and the incidence and metastasis of cancer. For this purpose, a comprehensive search was conducted across multiple databases from their inception until March 3, 2023. This culminated in the selection of 15 original studies on various types of cancer, including a collective sample of 1,403 individuals. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were employed as statistical parameters to determine the association between plasma VWF and the incidence and metastasis of cancer. These were estimated using a random-effects model. The pooled data revealed that the plasma VWF levels of patients with cancer were significantly elevated compared with those of healthy controls (SMD, 0.98; 95% CI, 0.59–1.36), and a significant association was observed between plasma VWF levels and cancer metastasis (SMD, 0.69; 95% CI, 0.33–1.06). The symmetry of the Begg's funnel plots indicated that no significant bias was present in the analyses of VWF in cancer and its metastasis. In summary, the results of the present meta-analysis support the hypothesis that increased plasma VWF levels may serve as a biomarker for cancer and metastatic progression. [ABSTRACT FROM AUTHOR]

The article titled "[Retracted] miR-143-5p suppresses breast cancer progression by targeting the HIF-1α-related GLUT1 pathway" was published in Oncology Letters in 2022. However, a concerned reader brought to the attention of the Editorial Office that some of the data presented in Figure 6F had already been published in a different paper by different authors. As a result, the Editor decided to retract the article from the journal. The authors were asked for an explanation but did not respond. The Editor apologizes for any inconvenience caused. [Extracted from the article]

Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway. [ABSTRACT FROM AUTHOR]

The C-X-C motif chemokine ligand 8 (CXCL8)-C-X-C chemokine receptor (CXCR)1/2 signalling axis is among numerous mechanisms which stimulate the immune system to defend against tumour growth and influence the tumour microenvironment to promote tumour growth. This pathway plays an important role in the development of a number of cancers including breast cancer (BC). The aim of the present study was to analyse the levels of the chemokine CXCL8 and its receptors, CXCR1 and CXCR2, in the serum of female patients with invasive BC and to assess the expression of these parameters at the mRNA level, considering molecular subtypes and degrees of cancer malignancy. The study group consisted of 62 patients with histopathologically confirmed invasive BC. The control group consisted of 18 patients with histopathologically confirmed fibroadenoma, a benign breast tumour. The levels of CXCL8, CXCR1 and CXCR2 were determined by sandwich ELISA using the CLOUD-CLONE ELISA kit. CXCL8, CXCR1 and CXCR2 transcript levels were analysed using reverse transcription-quantitative PCR. Results showed that serum CXCL8 levels in female patients with invasive BC were significantly higher compared with those in the control group (P<0.05). In addition, significantly elevated CXCR1 levels were observed in luminal B human epidermal growth factor receptor 2+ carcinoma compared with those in the control group. Analysis of CXCL8 in the serum of female patients with BC showed a statistically significant difference between clinical stage G1 and G2 (P<0.05), G2 and G3 (P<0.01), and G1 and G3 (P<0.0001). On the other hand, the analysis of CXCR1 and CXCR2 levels in the serum of the patients revealed a statistically significant difference between G2 and G3 (P<0.05). The current study showed that abnormalities in the immune response involving the CXCL8-CXCR1/2 signalling axis in patients with invasive BC are involved in the development of these tumours. Moreover, the demonstrated severity of changes occurring at protein level may suggest the potential usefulness of their determination as potential diagnostic markers in the clinic. [ABSTRACT FROM AUTHOR]

Lung cancer is associated with high morbidity and mortality rates. Forkhead box P2 (FOXP2) functions as an antitumor gene in various cancers. However, its role in lung cancer remains to be elucidated. The present study explored the potential role of FOXP2 in lung cancer. mRNA levels and protein expression were determined using RT-qPCR and western blotting, respectively. Functional analysis was performed using the CCK-8, Transwell and TUNEL assays. FOXP2 expression was downregulated in lung cancer. Notably, FOXP2 suppressed the proliferative, migratory and invasive abilities of lung cancer cells and promoted tumor cell apoptosis. In addition, FOXP2 blocked TGFβ signaling. However, SRI-011381-stimulated activation of TGFβ signaling reversed the effects of overexpressed FOXP2 and promoted the aggressiveness of lung cancer cells. FOXP2 functions as an antitumor gene in lung cancer cells. FOXP2 suppressed the malignant behavior of lung cancer by inactivating TGFβ signaling. [ABSTRACT FROM AUTHOR]

Exosomes carry functional molecules that can regulate cancer progression. Understanding the function of exosomal markers may provide invaluable insights into the mechanism of metastasis in hepatocellular carcinoma (HCC). The aim of the present study was to identify metastasis-associated microRNAs (miRNAs/miRs) expressed in plasma exosomes. A miRNA microarray and reverse transcription-quantitative PCR were used to analyze the plasma exosome miRNA expression profiles of patients with metastatic or non-metastatic HCC. Receiver operating characteristic (ROC) curve and Kaplan-Meier analyses were used to evaluate the predictive performance and prognostic effi- cacy of candidate miRNAs identified in the Gene Expression Omnibus database (dataset accession no. GSE67140). Bioinformatics analysis was used to examine the role of exosomal miRNAs in HCC metastasis. A total of 32 miRNAs were differentially expressed in plasma exosomes of patients with metastatic HCC compared with in those of patients with non-metastatic HCC. Additionally, the expression levels of six miRNAs were consistent between plasma exosome samples and matched tissue samples. ROC analysis demonstrated that miR-18a, miR-27a and miR-20b could discriminate metastatic HCC from non-metastatic HCC. Furthermore, the prognostic efficacy of the combination of three miRNAs (miR-18a, miR-20b and miR-221) was superior to that of individual miRNAs. Survival analysis demonstrated that high expression levels of the candidate miRNAs were associated with poor prognosis. Bioinformatics analysis indicated that the potential target genes of these miRNAs were involved in biological processes, molecular functions and cellular components that were associated with metastasis. The present findings suggested that these exosomal miRNAs may serve important roles in HCC lung metastasis and could represent a complementary clinical tool for the assessment of HCC prognosis. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the major causes of cancerassociated mortality worldwide. miR-1307-3p has been demonstrated to serve multiple roles in the development of various types of cancer. The present study aimed to evaluate the expression and functional role of miR-1307-3p in the progression of gastric cancer. The expression of miR-1307-3p in gastric cancer tissues and cell lines was detected by reverse transcription quantitative PCR. Furthermore, the correlation between miR-1307-3p expression and the clinicopathological characteristics and prognosis of patients was evaluated. Cell Counting Kit-8 and Transwell assays were performed to analyze the effects of miR-1307-3p on the proliferation and the migratory and invasive abilities of gastric cancer cells, respectively. Dual-luciferase reporter assay was conducted to reveal the potential underlying mechanism of miR-1307-3p. In gastric cancer tissues and cells, miR-1307-3p expression was significantly upregulated compared with the normal tissues and cell lines. In addition, the expression of miR-1307-3p was associated with the Tumor-Node Metastasis stage of patients. The results from Cox regression analysis demonstrated that miR-1307-3p may serve as an independent predictor for the prognosis of patients with gastric cancer. Furthermore, the upregulation of miR-1307-3p in gastric cancer cell lines significantly promoted the cell proliferation and migratory and invasive abilities by targeting DAB2 interacting protein. In conclusion, the findings from the present study suggested that miR-1307-3p may serve as a tumor promoter of gastric cancer and that miR-1307-3p expression in tumor tissues may be used as a prognostic indicator for patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third most common cause of cancer-associated mortality worldwide. Hepatectomy and liver transplantation are the main treatments for early HCC. Immunotherapy and targeted therapy for advanced HCC have become increasingly popular; however, their clinical benefits are limited. Thus, identification of novel therapeutic targets for advanced HCC remains essential. Fibrillarin (FBL) is an essential nucleolar protein that catalyzes the 2'-O-methylation of ribosomal RNAs. Recently, experimental data have suggested that FBL can influence breast-cancer progression. However, the association between FBL expression and HCC remains known. In the present study, the UALCAN database was used to assess FBL mRNA expression in HCC. Immunohistochemistry analysis was performed to detect FBL protein expression in 139 patients with HCC. In addition, bioinformatic analysis was performed using the UALCAN, the Database for Annotation, Visualization and Integrated Discovery, cBioportal and TargetScan databases. Data were analyzed using Kaplan-Meier curves and the log-rank test, and a Cox proportional hazards regression model. The results demonstrated that FBL expression was significantly higher in tumor tissues compared with para-tumor tissues. Furthermore, high FBL expression was significantly associated with tumor diameter and advanced TNM stage in HCC. High FBL expression also predicted a shorter overall survival time and disease-free survival time in patients with HCC. Bioinformatics analysis demonstrated that FBL may be regulated by methylation modification. In addition, analyses of functional annotations using the Gene Ontology database indicated that FBL-related genes were predominantly enriched in DNA repair and proliferation-related cell-signaling pathways. Notably, high FBL expression signified larger tumor diameter, advanced tumor stage and a poor prognosis. Taken together, the results of the present study suggest that FBL may be a potential target for HCC treatment. [ABSTRACT FROM AUTHOR]

Esophageal cancer is the eighth most prevalent malignancy in the world and China has a high incidence of esophageal cancer. Previous studies have identified that LINC00488 is an oncogene; however, its role in esophageal cancer remains unclear. The present study detected the expression and biological functions of LINC00488 in the progression of esophageal cancer. LINC00488 levels in 45 esophageal cancer and matched paracancerous tissues were detected. The association between LINC00488 level, clinical indexes and overall survival rate of patients with esophageal cancer was analyzed. Using Cell Counting Kit-8, Transwell and wound healing assays, the influence of LINC00488 on the biological functions of OE19 and OE33 cells were assessed. The target gene of LINC00488, microRNA-485-5p (miRNA-485-5p), was predicted using bioinformatics databases. In addition, the role of miRNA-485-5p in the progression of esophageal cancer was evaluated using rescue experiments. LINC00488 was upregulated in esophageal cancer tissues and cell lines. A high level of LINC00488 was associated with lymphatic and distant metastasis and poor prognosis in patients with esophageal cancer. Silencing LINC00488 attenuated the viability, migration and wound healing of OE19 and OE33 cells. miRNA-485-5p was downregulated in esophageal cancer and low expression levels predicted a poor prognosis in these patients. In addition, miRNA-485-5p level was negatively correlated with that of LINC00488. Rescue experiments showed that knockdown of miRNA-485-5p reversed the attenuated proliferation and migration of esophageal cancer cells with LINC00488-knockdown. In conclusion, LINC00488 aggravated the malignant progression of esophageal cancer by targeting miRNA-485-5p. [ABSTRACT FROM AUTHOR]

Ovarian cancer ranks 7th among the most common cancer types affecting women worldwide. A number of studies have confirmed that multiple long non-coding RNAs participate in the occurrence and progression of ovarian cancer. Small nucleolar RNA host gene 9 (SNHG9) serves a role in the progression of glioblastoma and pancreatic cancer. However, the specific biological function of SNHG9 in ovarian cancer has not yet been fully investigated. The present study aimed to determine the biological role and potential molecular mechanism underlying the influence of SNHG9 in ovarian cancer. SNHG9 expression in ovarian cancer cell lines and tissues were measured via reverse transcription-quantitative PCR analysis, and cell proliferation was detected via Cell Counting Kit-8 and colony formation assays. Flow cytometry was performed to assess cell cycle progression, and Transwell and wound healing assays were performed to assess cell invasion and migration abilities. Bioinformatics software was utilized to determine the target genes of SNHG9, which were subsequently verified via dual-luciferase reporter and RNA immunoprecipitation assays. The results demonstrated that SNHG9 expression was remarkably lower in ovarian cancer cell lines and tissues compared with the negative controls. Cell function assays demonstrated that decreased SNHG9 expression notably induced the migration, colony formation, proliferation and invasiveness of ovarian cancer cells. Furthermore, the inhibitory effect of SNHG9 on the migration, colony formation, proliferation and invasion of ovarian cancer cells was partially reversed by miR-214-5p upregulation. Thus, taken together, the current results suggest that SNHG9 may serve as a tumor suppressor gene in ovarian cancer by regulating the miR-214-5p/cryptochrome circadian regulator 2 axis. [ABSTRACT FROM AUTHOR]

A majority of cervical cancers are squamous cell carcinomas, arising from the squamous (flattened) epithelial cells that line the cervix. Long noncoding RNAs (lncRNAs) are a unique class of messenger RNA-like transcripts of at least 200 nucleotides in length with no significant protein-coding capacity. Aberrant lncRNA expression is emerging as a major component of the cancer transcriptome. In the present study, lncRNA microarrays were conducted to investigate the differentially expression lncRNAs in cervical cancer (CC) tissues compared with peritumoral tissues. Then, the most signifi- cantly upregulated lncRNA, which was lncRNA-AK001903 was selected to conduct further experiments. Real-time Quantitative polymerase chain reaction was conducted to investigate lncRNA-AK001903 expression in CC tissues and Hela, Siha, Ca Ski, C33a, H8 (HPV-immortalized cervical epithelial cell line) cell lines, and in situ hybridization histochemistry (ISHH) was performed to detect lncRNA-AK001903 expression level in different CC stages. The effect of lncRNA-AK001903 on cell proliferation, invasion and migration was assessed after knockdown of lncRNA-AK001903. The findings of the study confirmed that lncRNA-AK001903 was upregulated in CC cells and tissues compared with normal cell line H8 and peritumoral tissues. ISHH demonstrated that the expression level of lncRNA-AK001903 was connected with International Federation of Gynecology and Obstetrics (2018) stage of CC. Knockdown of lncRNA-AK001903 inhibited cell proliferation, invasion and migration in Ca Ski cells. In conclusion, lncRNA-AK001903 was demonstrated to be an oncogenic lncRNA that promotes tumor progression and may be an effective target for CC treatment in the near future. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are the most abundant population type of tumor-infiltrating immune cells found in the tumor microenvironment (TME), and are evolutionarily associated with microvessel density in tumor tissues. TAMs can be broadly divided into M1-like and M2-like TAMs, which demonstrate antitumor and pro-tumor activity in the TME, respectively. Studies have indicated that: i) The predominate presence of M2-like TAMs in the TME can result in tumor immunosuppression and chemoresistance; ii) the ratio of M1-like to M2-like TAMs in the TME is positively correlated with better long-term prognosis of patients with cancer; iii) epigenetic silencing, preventing the secretion of M1-like TAM-associated molecules, is an important immune evasion mechanism during tumor progression; and iv) the transformation from M2-like to M1-like TAMs following exposure to specific conditions can result in tumor regression. The present study discusses the molecular events underlying the recruitment of macrophages and their polarization into M1-like or M2-like TAMs, and their differential roles in angiogenesis, angiostasis, invasion, metastasis and immune activity in the TME. This insight may inform the improved design of TAM-targeted cancer immunotherapy. Some of these therapeutic strategies show promising effects; however, challenges remain. [ABSTRACT FROM AUTHOR]

The underlying causes of esophageal cancer (EC) are unknown. To explore the molecular mechanisms that lead to EC, gene expression profiles of large cohorts of patients with EC were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus (GEO) databases (GSE5364, GSE20347 and GSE23400). The present study identified 83 upregulated and 22 downregulated genes between EC and normal tissue using R statistical software and the GEO2R web tool. The Database for Annotation, Visualization and Integrated Discovery was used to identify the associated pathways, and for functional annotation of the differentially expressed genes (DEGs). Protein-protein interactions of these DEGs were analyzed based on the Search Tool for the Retrieval of Interacting Genes database, and hub genes were visualized using Cytoscape software. An online Kaplan-Meier plotter survival analysis tool was utilized to evaluate the prognostic value of hub gene expression in patients with EC. Further analysis of an additional dataset from GEO (GSE21293) revealed that these genes were associated with infiltration and metastasis in EC. In addition, the Gene Expression Profiling Interactive Analysis tool was used to evaluate expression levels of hub genes in patients with EC for different pathological stages. The Ualcan analysis tool was used to evaluate the expression levels of hub genes for different histological types. Overall, ubiquitin conjugating enzyme E2 C, cyclin dependent kinase inhibitor 3, CDC28 protein kinase regulatory subunit 2, kinesin family member 20A (KIF20A) and RAD51 associated protein 1 (RAD51AP1) were upregulated in EC tissues compared with normal tissues, and upregulation of these genes was a poor prognostic factor for patients with EC, indicating that these genes may mediate EC cell infiltration and metastasis. Among the hub genes, KIF-20A had potential value for predicting the pathological stage of EC. KIF20A and RAD51AP1 were more informative biomarkers of esophageal squamous cell carcinoma. Further studies are required to explore the value of these genes in the treatment of EC. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the leading causes of cancer‑associated deaths with incidence rates continuously on the rise. Biomarkers are urgently required for early diagnosis and better prognostic classification, which is essential for risk stratification and optimizing treatment strategies in clinical settings. By analyzing the data extracted from The Cancer Genome Atlas database using R, the long noncoding RNA (lncRNA) β‑site APP‑cleaving enzyme 1 antisense (BACE1‑AS) was discovered to have both high diagnostic and prognostic values in liver cancer, which could serve as a promising biomarker in clinical settings. Precisely, lncRNA BACE1‑AS i s s ignificantly o verexpressed i n l iver c ancer and its levels vary within different subgroups, suggesting its tumorigenic role. Furthermore, higher BACE1‑AS predicts poorer overall survival and relapse‑free survival outcomes. Overall, the present study demonstrated that BACE1‑AS may be involved in liver cancer progression and could serve as a promising biomarker for diagnosis and prognostic evaluation. [ABSTRACT FROM AUTHOR]

Transmembrane proteins are involved in the transportation of materials into and out of cells. The transmembrane protein (TMEM) family is a collection of poorly described transmembrane proteins that serve important roles in tumor development and progression. A number of TMEM proteins have been discovered. A newly discovered TMEM protein, TMEM206, transports ions across the membrane under physiological and pathological conditions, generating an acidic environment, which serves an important role in the microenvironment. However, the prognostic value and regulatory mechanisms of action of TMEM206 in tumors is unclear. The aim of the present study was to evaluate the prognostic value and regulation mechanisms of TMEM206 in tumors. Firstly, the expression of TMEM206 in tumors and normal tissues was assessed using the GEPIA and Oncomine databases and the results revealed that TMEM206 expression increased or decreased depending on the type of tumor. Subsequently, using the Human Protein Atlas and the Kaplan-Meier plotter, the findings of the present study revealed that TMEM206 is related to the prognosis of hepatocellular carcinoma. In order to explore the mechanism of TMEM206 in promoting tumor progression, GEO and cBioPortal were used to determine genes that may be co-expressed with TMEM206. MetaScape was used to identify the signaling pathways that TMEM206 may participate in. Finally, miRWalk, miRDB and TargetScan were used to identify miRNAs that may regulate the expression of TMEM206 and the findings revealed that 2 miRNA (hsa-miR-325 and hsa-miR-510-5p) were involved. In conclusion, upregulation of TMEM206 is associated with poor prognosis in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Compared to tumors of other organs, pancreatic cancer is highly aggressive; with one of its biological features being that, despite a prominent fibrotic stroma, there is remarkable infiltration of tumor cells. This characteristic is considered to be the main reason for the poor prognosis of patients with pancreatic cancer. Therefore, in order to elucidate the factors that contribute to this high invasiveness, a selective invasion method was used to establish four highly invasive subclones from six human pancreatic cancer cell lines. The results demonstrated that two cell lines did not exhibit enhanced invasiveness. Microarray analysis revealed that, in the highly invasive cell lines, several genes were expressed at high levels, compared with the original cell lines. These highly expressed genes were recognized only in highly invasive cells. Among them, IL-32 was most strongly upregulated in the highly invasive cells, compared with cells with a low invasive potential, as well as the original cells. RT-qPCR and western blot analysis confirmed the high levels of expression of IL-32 in highly invasive cells at the RNA and protein levels. In addition, immunohistochemical analysis of resected surgical materials revealed that the tumor cells expressed IL-32 and, in particular, many IL-32 positive cells were seen at the invasive front of the tumor tissue. IL-32 is a cytokine that is widely involved in the development of cancer and has recently received considerable attention. This cytokine has multiple splice variants and shows a wide variety of behaviors, depending on the tumor type and primary organ. Although some hypotheses have been proposed to explain the activity of IL-32, a unified view has not been agreed. In the present study, through the establishment of highly invasive cells from pancreatic cancer and a comprehensive gene analysis, it is suggested that IL-32 may serve an important role as a molecule involved in the invasiveness of this neoplasm. [ABSTRACT FROM AUTHOR]

Ring box protein-1 (RBX1) is an essential component of the S-phase kinase-associated protein, Cullin and F-box containing ubiquitin ligases. Overexpression of RBX1 has been reported in several cancer types; however, little is known regarding the prognostic value and role of RBX1 in esophageal cancer. The present study examined 120 patients with esophageal cancer (EC) who underwent curative esophagectomy and 61 patients with EC who underwent neoadjuvant combination chemotherapy with docetaxel, cisplatin and 5-fluorouracil (5-FU; DCF) using immunohistochemistry. All specimens were classified into two groups according to the percentage of RBX1-positive tumor cells. In addition, the impact of RBX1 expression on cancer cell proliferation was analyzed in vitro using a small interfering RNA silencing technique. RBX1 expression levels showed significant differences according to tumor size (P<0.001), tumor depth (P=0.002), lymph node metastasis (P=0.004), pathological stage (P=0.001), lymphatic invasion (P=0.001) and venous invasion (P=0.001). The overall survival (OS) rate in the RBX1 high expression group was significantly lower compared with that in the low group (P=0.004). Multivariate analysis demonstrated that RBX1 status was an independent prognostic factor. RBX1 gene silencing inhibited the proliferation of human EC cells and enhanced the antitumor effect of 5-FU. Among patients who underwent neoadjuvant DCF therapy, the RBX1 high expression group had a significantly lower OS rate compared with that of the RBX1-low group (P<0.001). In conclusion, RBX1 has notable prognostic value, and RBX1 may serve an important function in the tumor progression of EC. [ABSTRACT FROM AUTHOR]

Liver cancer (LC) is one of the primary contributors of cancer-associated death worldwide. Long non-coding RNAs (lncRNAs) have been shown to participate in almost every aspect of cell biology and serve fundamental roles in carcinogenesis and cancer progression, including in LC. However, the clinical significance and functional role of the lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) in LC have not yet been identified. The present study measured the expression levels of BCAR4 in LC cells and tissues, and discovered that BCAR4 was upregulated in LC tissues compared with adjacent normal tissues. Furthermore, high BCAR4 expression was associated with the presence of multiple tumors and advanced Tumor-Node-Metastasis stages (III/IV). Survival analysis found that high BCAR4 expression indicated poor overall survival (OS) and progression-free survival (PFS). By analyzing the risk factors of poor OS and PFS using univariate analysis and multivariate analysis, high BCAR4 expression was revealed to be an independent risk factor of poor prognosis. In addition, the role of BCAR4 was further investigated in vitro, which revealed overexpression of BCAR4 to markedly promote the proliferation, migration and invasion of LC cells. Conversely, the loss of BCAR4 expression repressed the proliferation, migration and invasion of LC cells. In conclusion, BCAR4 is overexpressed in LC and is associated with LC progression. Therefore, BCAR4 may be used as a potential prognostic marker in LC. [ABSTRACT FROM AUTHOR]

p21-activated kinase 6 (PAK6), a member of the serine/threonine kinase family, has been reported to be involved in numerous types of cancers. The present study aimed to investigate the role of PAK6 in cervical cancer. In the present study, PAK6 expression was evaluated in tissue microarrays and cell lines by using immunohistochemistry and western blotting. The mRNA level of PAK6 was evaluated by reverse transcription quantitative PCR. The Wnt/β-catenin signaling-related protein expression was detected by western blotting following short hairpin (sh)RNA-mediated PAK6 knockdown or PAK6 overexpression. Cell proliferation was determined using Cell Countink Kit-8. Migration, invasion and colony formation were further assessed following PAK6 knockdown or overexpression. Co-immunoprecipitation (Co-IP) and fluorescence colocalization microscopy were used to detect the interaction between PAK6 and GSK3β. The results from tissue microarray revealed that the expression levels of PAK6 in cervical cancer tissues were upregulated. The downregulation of PAK6 expression levels using shRNA not only decreased cell growth and proliferation, but it also inhibited the migration and invasion of HeLa cells. Conversely, the overexpression of PAK6 promoted the proliferation, migration and invasion of HeLa cells. In addition, the expression levels of proteins involved in the Wnt/β-catenin signaling pathway were modified in the PAK6 knockdown group, including downregulation of GSK3β phosphorylation and Cyclin D1 protein, and upregulation of β-catenin phosphorylation and E-cadherin. In contrast, following the overexpression of PAK6, the Wnt/β-catenin signaling pathway was activated. Further investigation using fluorescence microscopy and Co-IP assays indicated that PAK6 may interact with GSK3β. In conclusion, the findings of the present study suggested that PAK6 may serve a role in promoting cervical cancer through activating the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the fourth most lethal malignancy and is the second most common cause of cancer-associated mortality worldwide. The development of high-throughput sequencing has enabled the identification of potential biomarkers for the diagnosis and treatment of various types of cancer. Although microRNA-101 (miR-101) has been demonstrated to be a potential biomarker of CRC, its detailed mechanisms remain to be fully discovered. In the present study, overall survival analysis was applied to determine the association between miR-101 and CRC prognosis. Reverse transcription-quantitative PCR (RT-qPCR) was used to examine gene expression levels in tissues and cells. Cell proliferative and apoptotic activities were determined by MTT and flow cytometry assays, respectively. Wound healing and Transwell assays were used to examine CRC cell migration and invasion, respectively. In the present study, RT-qPCR analysis indicated that miR-101 was significantly downregulated in CRC tissues and cells. However, clinical data collected from The Cancer Genome Atlas revealed no significant association between the expression levels of miR-101 and the prognosis of CRC. Additionally, miR-101 inhibited the progression of CRC by directly binding to the 3′-untranslated region of Ras-related protein Rap1b (Rap1b). This was associated with downregulation of Rap1b expression. Furthermore, the overexpression of Rap1b promoted miR-101 mimic-attenuated CRC cell progression. The present study demonstrated that miR-101 may be involved in the repression of the CRC progression by forming a negative feedback loop with Rap1b. The findings revealed the interaction between miR-101 and Rap1b during the progression of CRC, which could aid the development of therapeutic strategies. [ABSTRACT FROM AUTHOR]

Hypoxia, an important component of the tumor microenvironment, plays a crucial role in the occurrence and progression of cancer. However, to the best of our knowledge, a systematic analysis of a hypoxia-related prognostic signature for breast cancer is lacking and is urgently required. Therefore, in the present study, RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and served as a discovery cohort. Cox proportional hazards regression analysis was performed to construct a 14-gene prognostic signature (PFKL, P4HA2, GRHPR, SDC3, PPP1R15A, SIAH2, NDRG1, BTG1, TPD52, MAFF, ISG20, LALBA, ERRFI1 and VHL). The hypoxia-related signature successfully predicted survival outcomes of the discovery cohort (P<0.001 for the TCGA dataset). Three independent Gene Expression Omnibus databases (GSE10886, GSE20685 and GSE96058) were used as validation cohorts to verify the value of the predictive signature (P=0.007 for GSE10886, P=0.021 for GSE20685, P<0.001 for GSE96058). In the present study, a robust predictive signature was developed for patients with breast cancer, and the findings revealed that the 14-gene hypoxia-related signature could serve as a potential prognostic biomarker for breast cancer. [ABSTRACT FROM AUTHOR]

Extravasated platelet aggregation (EPA) serves an important role in the cancer microenvironment during cancer progression, and has been demonstrated to interact with tumor cells in several types of cancer. EPA induces epithelial-mesenchymal transition (EMT) via transforming growth factor-β, and also recruits immunosuppressive cells, including regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). However, the role of EPA in gastric cancer with peritoneal metastasis remains unknown. The present study analyzed the association between EPA and prognosis in patients with gastric cancer with peritoneal metastasis. The present study evaluated 62 patients diagnosed with advanced gastric cancer with peritoneal metastasis between 2001 and 2016. EPA, EMT, Treg cells and MDSCs in peritoneal metastatic lesions were detected by immunohistochemical evaluation of CD42b, SNAIL, FOXP3 and CD33, respectively. CD42b expression was observed in 56.5% (35/62) of peritoneal metastatic lesions. CD42b expression in peritoneal metastatic lesions was associated with poor overall survival compared with lower frequencies (hazard ratio, 2.03; 95% confidence interval, 1.12–3.69; P=0.018). SNAIL, FOXP3 and CD33 expression were not associated with overall survival, but CD33 expression was markedly higher in CD42b-positive patients (P=0.022). These results indicated that EPA affects immunosuppression by recruiting MDSCs in the tumor microenvironment via the secretion of soluble factors, resulting in tumor progression. EPA may be a novel therapeutic target for gastric cancer with peritoneal metastasis. [ABSTRACT FROM AUTHOR]

Ubiquitin-conjugating enzyme E2T (UBE2T) is a recently discovered oncogenic protein. Numerous studies reported that UBE2T is highly expressed in various types of human cancer; however, its role in the carcinogenesis and progression of pancreatic cancer remains unknown. The aim of the present study was to investigate the role of UBE2T in pancreatic cancer progression through in vitro experiments in pancreatic cancer tissues and cell lines. The results obtained in the present study demonstrated that UBE2T served an important role in the initiation and progression of pancreatic cancer. Furthermore, increased expression of UBE2T in human pancreatic cancer tissues and pancreatic cancer cells was observed compared with normal tissues and cells. The effect of upregulating and downregulating UBE2T in pancreatic cancer cell lines was investigated using the MTT, wound-healing and migration and invasion assays. The results demonstrated that overexpression of UBE2T significantly promoted pancreatic cancer cell proliferation, migration and invasion compared with controls. However, UBE2T downregulation resulted in the inhibition of pancreatic cancer cell proliferation, migration and invasion. In addition, the results demonstrated that UBE2T may promote the epithelial mesenchymal transition in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, due to poor diagnosis and treatment. There is increasing evidence that demonstrates the involvement of long non-coding RNAs (lncRNAs) in carcinogenesis and cancer progression. Therefore, the aim of the present study was to explore potential lncRNA-associated features of patients with OSCC as a valuable and independent prognostic biomarker. A total of 268 lncRNA expression profiles and clinical patient information on OSCC were downloaded from The Cancer Genome Atlas database. The clinical information was exploited for prescreening, using Cox regression analysis, and differentially expressed lncRNAs (DElncRNAs) were identified using edgeR software. Using the 'caret' package, the datasets were categorized into test datasets and training datasets, respectively. Through bioinformatics, seven prognostic DElncRNAs were selected. Using the regression coefficients, a risk score based on the seven-DElncRNA signature was developed to assess the prognostic function of key DElncRNAs. According to the median risk score, patients were classified into high-risk and low-risk groups in the training and test datasets. Additionally, receiver operating characteristic (ROC) curve analysis was conducted to evaluate the sensitivity and specificity of the prognostic DElncRNAs, and the optimal cut-off point was obtained from ROC analysis. Based on the optimal cut-off point, the patients were also categorized into high-risk and low-risk groups. Notably, the optimal cut-off point was more sensitive than the median risk score, particularly in the test dataset. The Kaplan-Meier survival and log rank test analysis results indicated that the P-value, based on the optimal cut-off, was less than the median risk cut-off. Additionally, stratified analysis results revealed that the seven-DElncRNAs signature was also independent of OSCC age. Furthermore, the findings of the present study suggested that the seven-DElncRNA signature can be used as a potential prognostic indicator and may have important clinical significance in OSCC. [ABSTRACT FROM AUTHOR]

The molecular mechanisms involved in the development and progression of colorectal cancer (CRC) are not completely understood. The present study aimed to identify potential novel genes involved in the development and progression of CRC. Database analysis revealed that the mRNA level of the chloride channel accessory 4 (CLCA4) was frequently lower in primary tumor tissues compared with that in corresponding non-cancerous colon tissues, and was even lower in liver metastases than in primary tumors. Further analyses through The Human Protein Atlas (THPA) website and immunohistochemistry (IHC)-based tissue microarray (TMA) confirmed that CLCA4 mRNA and protein expression were downregulated in CRC tissues. Furthermore, IHC-based TMA analysis revealed a gradual decrease in CLCA4 protein expression among colorectal normal, adenoma and carcinoma tissues. Survival analysis revealed that the decrease in CLCA4 mRNA expression was associated with the overall survival rate of patients with different types of tumor, including CRC, breast cancer, head and neck cancer and stomach cancer. Overall, downregulated CLCA4 expression may influence the development and progression of CRC. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common cancer types in the world. This study was carried out to investigate the functional role of circular RNA circ_103809 in breast cancer. The expression of hsa_circ_103809 in breast cancer tissues and breast cancer cells were verified. After transfection, the expression of hsa_circ_103809 in the cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and colony formation assay were used to detect cell proliferation. Apoptosis and cell cycle were detected by flow cytometry. AKT, p-AKT, BCL2 and Bax were detected by western blotting. Tumor formation assay was employd in vivo. The expression of circ_103809 in breast cancer was overexpressed. circ_103809 was proved to promote cell proliferation in breast cancer progression. In addition, circ_103809 was also involved in repressing cell apoptosis and accelerating cell cycle progression in vitro. circ_103809 accelerated breast cancer progression via regulating PI3K/AKT signaling. circ_103809 promoted tumor formation in vivo. The circular RNA hsa_circ_103809 was highly expressed in breast cancer tissues and cells, and may play an oncogene role in the development of breast cancer, and is expected to become a new target for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common carcinomas with high morbidity and mortality worldwide. However, the underlying molecular mechanisms of CRC are unclear. The aim of the present study was to establish the role that overexpression of LBX2 serves in CRC and to investigate the associated biological pathways. The difference in the expression levels of LBX2 between CRC tissues and adjacent normal colorectal tissues was assessed using the Oncomine database and Tumor Immune Estimation Resource. The expression levels of LBX2 and its prognostic significance in CRC were analyzed using a t-test and χ2 test using data from The Cancer Genome Atlas database. The Kaplan-Meier method and Cox regression analysis were used to estimate the prognostic value of LBX2 in CRC. Furthermore, the potential mechanisms of LBX2 dysregulation and its underlying molecular mechanisms in CRC were investigated using Gene Set Enrichment Analysis (GSEA). LBX2 expression levels were significantly upregulated in CRC samples compared with corresponding normal colorectal tissues (P<0.05). LBX2 upregulation was correlated with advanced tumor stage (III or IV), vascular invasion, lymphatic invasion and the male sex (all P<0.05). Kaplan-Meier analyses showed that high expression levels of LBX2 were associated with a less favorable overall survival (OS) and disease-free survival (DFS) in CRC (all P<0.05). Multivariate analyses further confirmed that LBX2 upregulation was an independent indicator of less favorable OS and DFS (all P<0.05). In addition, LBX2 DNA hypomethylation and microRNA (miR)-378a-3p downregulation correlated with LBX2 upregulation in CRC (all P<0.05). The downregulation of miR-378a-3p in CRC was also significantly associated with less favorable OS and DFS, as demonstrated using Kaplan-Meier analyses (all P<0.05). Moreover, GSEA indicated that 'VEGF signaling', 'Cell adhesion molecules CAMs', 'Toll-like receptor signaling' and 'Natural killer cell-mediated cytotoxicity' signaling pathways were enriched in the high LBX2 expressing cohort (all P<0.05). Thus, overexpression of LBX2 may be associated with the development of CRC and may serve as a novel prognostic marker and therapeutic target in CRC. The mechanisms of LBX2 upregulation in CRC are possibly associated with LBX2 DNA hypomethylation and miR-378a-3p downregulation. The potential mechanisms of LBX2 upregulation in CRC might be regulated via the 'Cell adhesion molecules CAMs', 'Toll-like receptor signaling' and 'Natural killer cell-mediated cytotoxicity' signaling pathways. [ABSTRACT FROM AUTHOR]

Recently, a number of microRNAs (miRNAs) have been reported to play different roles in human cancers, including colorectal cancer (CRC). However, the specific role of miR-758 has not been clarified in CRC. Therefore, the aim of the present study was to explore the role of miR-758 in CRC. RT-qPCR and western blot analysis were used to quantify the expression of miR-758 and genes. The function of miR-758 in CRC was investigated using Transwell, CCK-8 and luciferase reporter assays. According to the results, the downregulation of miR-758 expression was associated with aggressive behavior and poor prognosis in CRC patients. miR-758 was shown to restrain the cell viability and metastasis in CRC. In addition, it was confirmed that miR-758 directly targets PAX6 and inhibits CRC progression through targeting PAX6. The results also revealed that miR-758 blocked EMT and PI3K/AKT pathway in CRC. In conclusion, miR-758 acts as a tumor suppressor in CRC by downregulating PAX6. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) exhibits the highest mortality among all urological malignancies. The investigation of the potential disease progression markers can improve ccRCC diagnosis and treatment. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is involved in carcinogenesis and cancer progression in a variety of cancer types including RCC. While, its role in ccRCC remains unclear, this cancer type is considered the most aggressive RCC subtype. In the present study, RT-qPCR, western blotting and immunohistochemical (IHC) assays demonstrated that GRIM-19 protein and mRNA levels were downregulated in ccRCC tumor tissues compared with the corresponding levels noted in paracancerous non-tumor tissues. The deficiency of this protein contributed in relaxed and/or collapsed structures of the kidney tubules and collecting duct noted in tumor tissues. Moreover, the reduction in GRIM-19 expression was associated with high tumor, lymph nodes and metastasis (TNM) stage and Fuhrman grade of ccRCC tumors. The data suggested that GRIM-19 acted as a tumor suppressor and that its deficiency promoted ccRCC development and progression. GRIM-19 can be considered a potential tumor marker for ccRCC. [ABSTRACT FROM AUTHOR]

The abnormal expression of cadherin-11 (CDH11) affects the progression of several types of cancer. However, the expression pattern and prognostic value of CDH11 in gastric cancer (GC) have not been reported. In the present study, the expression of CDH11 in patients with GC and its effect on their survival were analyzed using public cancer databases. The expression of CDH11 in GC tissues was significantly higher compared with that in normal gastric tissues. The expression of CDH11 was higher in advanced GC compared with early GC, and increased CDH11 was associated with tumor progression and poor prognosis in patients with GC. The high level of methylation in the promoter of CDH11 in GC tissues was not sufficient to reverse the upregulation of CDH11 caused by transcriptional activation. Finally, the expression pattern and prognostic significance of CDH11 in GC were validated using data from patients with GC recruited for the present study. Collectively, the present results demonstrated that CDH11 was upregulated in GC tissues, and suggested that high CDH11 expression may be associated with progression and poor prognosis in GC. [ABSTRACT FROM AUTHOR]

Potential function of LINC00460 in the progression of ovarian cancer (OC) and its underlying mechanism were studied. LINC00460 level in OC tissues and normal ovarian tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between LINC00460 level with tumor stage, tumor size and pathological subtypes of OC was analyzed. Potential influence of LINC00460 on proliferative ability and cell cycle progression was evaluated. In vivo tumorigenesis model was conducted by administration of A2780 cells transfected with sh-NC or sh-LINC00460 in nude mice. Predicted through JASPAR database, ZNF703 was screened out as the transcriptional factor binding to LINC00460 promoter region. Chromatin immunoprecipitation (ChIP) assay was performed to verify the binding relationship between ZNF703 and LINC00460. The potential role of ZNF703 in LINC00460-mediated OC progression was examined. LINC00460 was upregulated in OC tissues and cell lines. Its level increased with the deterioration of tumor stage and enlargement of tumor size. LINC00460 was highly expressed in serous ovarian cancer relative to other subtypes of OC. Knockdown of LINC00460 attenuated proliferative ability and arrested cell cycle of A2780 and HO8910 cells. ZNF703 was upregulated in OC tissues. ChIP assay showed pronounced enrichment of LINC00460 in ZNF703. Rescue experiments revealed that ZNF703 overexpression reversed the regulatory effects of LINC00460 on cellular behavior of OC cells. LINC00460 is upregulated in OC tissues and cell lines, which is closely related to tumor progression. It accelerates proliferative ability and cell cycle progression of OC cells via interacting with ZNF703. [ABSTRACT FROM AUTHOR]

Role of long non-coding RNA (lncRNA) PICART1 in alleviating the progression of cervical cancer (CC) via targeting TCF21 was elucidated. PICART1 level in CC and paracancerous tissues was determined by quantitative realtime polymerase chain reaction (qRT-PCR). Its level in CC patients with different tumor stages (stage I+II and stage III+IV) and tumor sizes (≤4 cm and >4 cm) was examined. Survival analysis was conducted in CC patients expressing high level and low level of PICART1. Changes in proliferative, migratory and invasive abilities of HeLa and SiHa cells after transfection of si-PICART1 were assessed. Prognostic value of TCF21 in CC was determined by Kaplan-Meier curves. The interaction between PICART1, TCF21 and ARID1A was investigated through RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assay. PICART1 was downregulated in CC tissues and cell lines. CC patients with worse TNM staging and larger tumor size presented lower level of PICART1. Low level of PICART1 in CC patients predicted a worse prognosis. Silence of PICART1 stimulated the proliferative, migratory and invasive abilities of HeLa and SiHa cells. TCF21 expression was low in CC tissues and positively regulated by PICART1. Low level of TCF21 in CC patients predicted a worse prognosis. Potential binding relationship was verified among PICART, ARID1A and TCF21. ChIP assay confirmed the decreased enrichment of ARID1A in TCF21 promoter region after PICART1 knockdown. lncRNA PICART1 recruits ARID1A to activate TCF21 expression, thus alleviating the malignant progression of CC. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) RNA methylation, which is related to cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators (including ‘writers’, ‘erasers’ and ‘readers’). However, the prognostic value of m6A RNA methylation regulators involved in hepatocellular carcinoma (HCC) carcinogenesis and progression remains to be elucidated. The aim of the present study was to determine the prognostic score in predicting the prognosis of HCC patients based on these regulators. In The Cancer Genome Atlas, most of the 13 major m6A RNA methylation regulators were found to be differentially expressed between HCC and normal samples (P<0.001). In addition, two subgroups (clusters 1/2) had also been identified by applying consensus clustering in the m6A RNA methylation regulators. As compared with the cluster 1 subgroup, the cluster 2 subgroup was correlated with a poorer prognosis, as shown by the Kaplan-Meier method (P=6.197e-4). A risk signature was constructed based on these findings using six m6A RNA methylation regulators, which could not only predict the clinicopathological features of HCCs, but also serve as an independent prognostic marker, as shown by Cox regression analysis (hazard ratio=1.219, 95% confidence interval: 1.143-1.299; P<0.001). Data from the International Cancer Genome Consortium were used for external validation. In addition, gene set enrichment analysis identified several pathways that m6A RNA methylation regulators were closely associated with. In conclusion, the m6A RNA methylation regulators are the crucial participants in the malignant progression of HCCs, which are potentially useful for prognosis stratification and therapeutic strategy development for HCC. [ABSTRACT FROM AUTHOR]

Cervical Cancer is one of the leading causes of cancer-associated mortality in women. The present study aimed to identify key genes and pathways involved in cervical cancer (CC) progression, via a comprehensive bioinformatics analysis. The GSE63514 dataset from the Gene Expression Omnibus database was analyzed for hub genes and cancer progression was divided into four phases (phases I-IV). Pathway enrichment, protein-protein interaction (PPI) and pathway crosstalk analyses were performed, to identify key genes and pathways using a criterion nodal degree ≥5. Gene pathway analysis was determined by mapping the key genes into the key pathways. Co-expression between key genes and their effect on overall survival (OS) time was assessed using The Cancer Genome Atlas database. A total of 3,446 differentially expressed genes with 107 hub genes were identified within the four phases. A total of 14 key genes with 11 key pathways were obtained, following extraction of ≥5 degree nodes from the PPI and pathway crosstalk networks. Gene pathway analysis revealed that CDK1 and CCNB1 regulated the cell cycle and were activated in phase I. Notably, the following terms, ‘pathways in cancer’, ‘focal adhesion’ and the ‘PI3K-Akt signaling pathway’ ranked the highest in phases II-IV. Furthermore, FN1, ITGB1 and MMP9 may be associated with metastasis of tumor cells. STAT1 was indicated to predominantly function at the phase IV via cancer-associated signaling pathways, including ‘pathways in cancer’ and ‘Toll-like receptor signaling pathway’. Survival analysis revealed that high ITGB1 and FN1 expression levels resulted in significantly worse OS. CDK1 and CCNB1 were revealed to regulate proliferation and differentiation through the cell cycle and viral tumorigenesis, while FN1 and ITGB1, which may be developed as novel prognostic factors, were co-expressed to induce metastasis via cancer-associated signaling pathways, including PI3K-Art signaling pathway, and focal adhesion in CC; however, the underlying molecular mechanisms require further research. [ABSTRACT FROM AUTHOR]

There is increasing evidence demonstrating that disorders affecting microRNAs (miRs) influence tumorigenesis and progression, which results in a poor prognosis in patients with breast cancer (BC). In the present study, the precise molecular mechanism underlying the role of miR-320 in the progression of BC was investigated. Reverse transcription-quantitative PCR was conducted to determine mRNA expression, and western blot analysis was used to test protein levels. An MTT assay was conducted to detect cell viability and Transwell assays were used to analyze cell migration and invasion abilities. Furthermore, E74-like factor 3 (ELF3) protein density was tested via immunohistochemistry. Tumor volume was detected by xenograft tumor formation assay. The current results indicated that miR-320 expression was downregulated in BC tissues and cells, and was associated with a poor prognosis of patients with BC. Overexpression of miR-320 inhibited cell proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition and the PI3K/AKT signaling pathway in BC cells. Furthermore, it was revealed that the tumor size and weight were smaller in nude mice that had been transfected to overexpress miR-320. The luciferase reporter assay demonstrated the direct binding of miR-320 to the 3' untranslated region of ELF3 mRNA, which may further downregulate ELF3. Overall, the present results provided evidence that miR-320 may be a tumor suppressor in BC, and that the miR-320/ELF3 axis regulated tumor progression via the PI3K/AKT signaling pathway, which may represent a novel treatment strategy for BC. [ABSTRACT FROM AUTHOR]

Bladder cancer is a common genitourinary carcinoma with high morbidity and mortality rates. Circular RNAs (circRNAs), which are a type of single-stranded RNAs, have been characterized as stable, conserved and tissue-specific molecules in mammalian cells. The present study explored the circRNA expression profile in four bladder cancer tissues and matched normal samples by using microarray analysis. Furthermore, bioinformatics analyses were performed to investigate the potential function of dysregulated circRNAs in bladder cancer. The results demonstrated that 89 circRNAs were downregulated and 210 circRNAs were upregulated in bladder cancer tissues. The results from RT-qPCR demonstrated that hsa_circ_100241, hsa_circ_100242 and hsa_circ_101303 were markedly upregulated whereas hsa_circ_104510 was significantly downregulated in bladder cancer tissues compared with normal tissue. Following circRNA/microRNA (miRNA) interaction network generation via Cytoscape, it was demonstrated that hsa_circ_100242 contained a miRNA response element for miR-145-5p, which is a tumor suppressor in bladder carcinoma. In addition, results from the Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling pathway was the most significant pathway of the differentially expressed circRNAs in bladder cancer tissues. In conclusion, the present study demonstrated that circRNAs were dysregulated in bladder cancer tissues compared with matched normal samples. Pathway analysis was also performed to predict the binding of miRNAs to the dysregulated circRNAs. The results revealed that hsa_circ_100242 may be involved in bladder cancer initiation and progression by sponging miR-145. These findings may provide further insights into the functional and therapeutic roles of circRNAs in bladder cancer. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGFβ) is a secreted cytokine whose aberrant spatiotemporal expression is related to cancer progression and metastasis. While TGFβ acts as a tumor suppressor in normal and premalignant stages, TGFβ functions as a tumor promoter during the malignant phases of tumor progression by prompting cancer cells to undergo epithelial-mesenchymal transition (EMT), which enhances tumor cell invasion and ultimately promotes metastasis to other organs. Extensive studies have been performed to uncover the molecular and cellular mechanisms underlying TGFβ inducing EMT in cancer cells. Here, we suggested that ELK3, which encodes a protein that orchestrates invasion and metastasis of triple negative breast cancer cells, is a downstream target of TGFβ-SMAD3 in MDA-MB231 cells. ELK3 expression was increased in a time-dependent manner upon TGFβ treatment. Chemical and molecular inhibition of the TGFβ receptor blocked the ability of TGFβ to induce ELK3 expression. Small interfering RNA-mediated suppression analysis revealed that SMAD3 induces TGFβ signaling to express ELK3. Moreover, the results of the luciferase reporter assay and chromatin immunoprecipitation analysis showed that SMAD3 directly binds to the SMAD-binding element on the promoter of ELK3 to activate gene expression following TGFβ stimulation. We concluded that ELK3 is a novel downstream target of TGFβ-SMAD3 signaling in aggressive breast cancer cells. [ABSTRACT FROM AUTHOR]

Role of long-chain non-coding ribonucleic acid (lncRNA) GACAT1 in the development of breast cancer and its possible mechanism were investigated. The levels of GACAT1, microRNA-875-3p and Stonin2 (STON2) in breast cancer tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The level of GACAT1 in breast cancer cell lines was further explored. The effects of GACAT1 and microRNA-875-3p on cell proliferation and cycle were detected by cell counting kit-8 (CCK-8) and flow cytometry. The binding relationship between microRNA-875-3p and STON2, microRNA-875-3p and GACAT1 was examined by a dual luciferase reporting assay. It was confirmed by rescue experiments whether GACAT1 canregulate the level of STON2 by binding to microRNA-875-3p. GACAT1 level was clearly enhanced in breast cancer tissues compared to that of the adjacent tissues. Similar result was observed in breast cancer cell lines. Upregulation of GACAT1 promoted the proliferation and cycle of breast cancer cells including MCF-7 and BCap-37. The dual luciferase reporting assay results indicated that GACAT1 had a binding relationship with microRNA-875-3p. Further experiments confirmed that microRNA-875-3p was conspicuously downregulated in breast cancer tissues, and upregulation of microRNA-875-3p could inhibit the proliferation ability of MCF-7 and BCap-37 cells, and partially reversed the promoting effect of GACAT1 on cell cycle. Through bioinformatics prediction and dual luciferase reporter gene experiments, we found that STON2 might be a target gene of microRNA-875-3p. Overexpression of STON2 could partially abolish the effect of microRNA-875-3p on cell proliferation and cycle of MCF-7 and BCap-37 cells. GACAT1 can participate in the progression of breast cancer by promoting the proliferation and cycle of breast cancer cells. The mechanism may be through the regulation of the level of STON2 by adsorbing microRNA-875-3p. [ABSTRACT FROM AUTHOR]

The chemokine CXCL10 and its receptor CXCR3 have been demonstrated to be implicated in cancer cell proliferation and metastasis. CXCR3 has three splice variants: CXCR3A, CXCR3B and CXCR3-alt. CXCR3A and B serve multiple roles in the growth and invasiveness of a number of cancer types. However, the roles of CXCR3 isoforms in colorectal cancer (CRC) cells remain unclear. In the current study, the effects of CXCL10 and CXCR3 isoforms on proliferation and invasion of CRC cells was examined. Proliferation and invasiveness of the CRC cell line HCT116, which were transfected with CXCR3A or CXCR3B in the presence of CXCL10, were evaluated in vitro using MTT, scratch wound healing and transwell assays. MTT assay indicated that regardless of the presence or absence of CXCL10, the proliferative ability of CXCR3A-transfected HCT116 cells was enhanced compared with blank and mock cells. Scratch wound healing and transwell assays indicated that invasiveness of CXCR3A-transfected cells was greater compared with blank and mock cells. However, HCT116 cells transfected with CXCR3B did not exhibit changes in their proliferative or invasive ability. mRNA expression of MMP9, which is associated with signaling downstream of the CXCL10/CXCR3A pathway, was increased 4-fold in CXCR3A-transfected HCT116 cells compared with control cells. The results of the present study indicated that CXCL10-enhanced proliferation and invasiveness of the CRC cell line HCT116 was likely mediated by CXCR3A, but not by CXCR3B. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify potential therapeutic targets that serve crucial roles in the progression of cervical cancer. Clinical data, RNA sequencing (RNAseq)-counts and micro (mi)RNA data regarding cervical squamous cell carcinoma were retrieved from The Cancer Genome Atlas, and analyses were performed using the University of California Santa Cruz database. RNAseq and miRNA data were stratified into 3 groups (according to the patients' age), and genes were re-annotated and preprocessed prior to Mfuzz time clustering analysis. Subsequently, enrichment analyses were performed in order to identify differentially expressed mRNAs (DEmRNAs) and a protein-protein interaction analysis network was constructed. miRNA-gene, miRNA-lncRNA, and long non-coding (lnc)RNA-mRNA pairs were collected and the lncRNA-miRNA-mRNA competing endogenous (ce)RNA network was established. Further enrichment analyses were performed in order to identify crucial mRNAs in the ceRNA network. Finally, survival and drug association analyses were implemented. A total of 269 DEmRNAs [including alcohol dehydrogenase 7 (ADH7), vestigial-like family member 3 (VGLL3) and cytochrome P450, family 26, subfamily B, polypeptide 1 (CYP26B1)], 274 DElncRNAs (including LINC01133) and 16 DEmiRNAs (including miR-3065 and miR-330) were identified. There were 102 lncRNAs, 15 miRNAs, 15 mRNAs and 522 interaction pairs in the ceRNA network. In particular, ADH7 was regulated by miR-3065, and miR-3065 interacted with LINC01133 in the ceRNA network. Furthermore, ADH7 and CYP26B1 were enriched in the retinoic acid metabolic process and the retinol metabolism pathway. ADH7 and VGLL3 were significantly associated with the cervical cancer survival rate. ADH7, VGLL3, CYP26B1, miR-3065, miR-330, miR-499a and LINC01133 play pivotal roles in the progression of cervical cancer in different age groups. [ABSTRACT FROM AUTHOR]

Immunotherapy is effective in improving the survival and prognosis of patients with non-small cell lung cancer (NSCLC), and identifying effective immunomarkers is important for immunotherapy. Interleukin (IL)-36γ is a novel immunomarker that has an important function in the antitumor immune response. The present study investigated the association between IL-36γ and NSCLC to provide novel insight into immunotherapy for patients with NSCLC. Tissue microarrays of lung adenocarcinoma and squamous cell carcinoma were purchased for immunohistochemical analysis of IL-36γ expression levels and clinical parameters. In addition, fresh clinical NSCLC and adjacent normal tissue samples were collected to analyze IL-36γ mRNA expression levels using quantitative PCR. IL-36γ protein was primarily located in the cytoplasm, with a small quantity in the nucleus, and IL-36γ mRNA and protein expression levels in lung cancer tissues were significantly higher compared with those in adjacent normal tissues. Elevated IL-36γ protein expression levels were significantly associated with a higher tumor grade of lung adenocarcinoma; however, IL-36γ mRNA expression levels were inversely associated with the clinical Tumor-Node-Metastasis stage in patients with lung squamous cell carcinoma. In addition, patients with adenocarcinoma with high IL-36γ protein expression levels tended to longer post-operative survival times. These findings indicate that IL-36γ may have potential as an immunomarker for prediction of tumor progression and survival in patients with NSCLC. [ABSTRACT FROM AUTHOR]

The Klotho (KL) gene was first identified as a potent aging suppressor. The KL family currently comprises of three proteins: α-Klotho (KLA), β-Klotho (KLB), and γ-Klotho (KLG). Many studies have shown that KLA and KLB participate in tumor progression or suppression, depending on the type of cancer; however, the relationship between KLG and prostate cancer has not yet been studied. Some studies have claimed that KL is correlated to sensitivity to chemotherapy. Here, we investigated the oncogenic potential of KLG in castration-resistant prostate cancer (CRPC). Immunohistochemical analysis using prostate biopsy specimens revealed that patients with high KLG expression in primary prostate cancer tissue had a significantly poor prognosis for overall survival. In addition, the prostate-specific antigen response rate after docetaxel (DTX) therapy in patients with high KLG expression was lower than that in patients with low KLG expression. To evaluate the potential of KLG as a therapeutic target in human prostate cancer, we generated a xenograft model of human CRPC cell line (PC-3) in male athymic mice. The animals were randomly divided into four groups as follows: i) control group (vehicle only); ii) DTX group (intraperitoneal administration); iii) small interfering RNA targeting KLG (KLG siRNA) group (intratumoral administration); and iv) a combination group (DTX plus KLG siRNA). After 3 weeks of treatment, the tumor weight and tumor Ki-67 labeling index were significantly lower in the KLG siRNA group and the combination group than in the control group. Sensitivity to DTX was increased upon treatment with KLG siRNA. These findings suggest that KLG expression in primary prostate cancer lesions is associated with resistance to DTX in CRPC and has potential as a diagnostic and therapeutic target for patients with CRPC. [ABSTRACT FROM AUTHOR]