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TIPE1 is a gene in the TNFAIP8 family involved in immune regulation and tumorigenesis. Although previous studies demonstrated that TIPE1 might play different roles in different tumors, its expression and role in lymphoma are unclear. Here we observed TIPE1 expression in diffuse large B cell lymphoma (DLBCL). Two microarrays containing 96 tumor tissue specimens were obtained from the Affiliated Hospital of Nantong University biobank. All specimens came from patients with a clear pathological diagnosis of lymphoma, lymphadenitis, breast cancer, or bladder cancer, and we performed immunohistochemical experiments on these tissue specimens. GEPIA and TIMER platforms were used for bioinformatic analyses. We found higher TIPE1 expression in tumor tissues from patients with lymphoma compared with those with lymphadenitis, breast cancer, or bladder cancer. The GEPIA and TIMER analyses revealed that TIPE1 was upregulated in DLBCL tissues but not in invasive breast carcinoma, urothelial bladder carcinoma, or liver hepatocellular carcinoma tissues. TIPE1 expression was irrelevant for pathological stage, overall survival, or DLBCL immune infiltration levels. However, TIPE1 expression was correlated with MKI67 expression in DLBCL. Overall, TIPE1’s high expression levels in DLBCL may contribute to tumor growth in DLBCL.

Taurine upregulated gene 1 (TUG1) has been implicated in the onset and progression of various malignancies. The current study aimed to evaluate the biological function and potential mechanisms of TUG1 in multiple myeloma (MM) progression. TUG1 knockdown in MM cells was investigated in vitro and in vivo to evaluate the role of TUG1. We also predicted the transcription factor (TF) that bound to TUG1 together with the downstream target genes of the TUG1-TF interaction, and evaluated the regulatory mechanism of TUG1 in cell assays. TUG1 knockdown reduced the cell's proliferative and migratory capabilities while increasing apoptosis and bortezomib sensitivity in vitro and inhibiting tumorigenesis in vivo. TUG1 was found in the nucleus of MM cells and was found to be positively regulated by the TF-YY1. Further in vitro mechanistic investigations indicated that the YY1-TUG1 complex targeted YOD1 to regulate MM progression. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer (CRC) is a common carcinoma of the gastrointestinal tract with high incidence and mortality worldwide. Studies have shown that long noncoding RNAs (lncRNAs) play important roles in CRC. Our purpose is to investigate the potential of serum Linc01836 as a diagnostic and prognostic marker in CRC. Methods: We evaluated the expression of Linc01836 via quantitative real-time polymerase chain reaction (qRT-PCR). The serum CEA, CA19-9, Cyfra21-1, and CA72-4 concentrations were measured by Architect I4000 SR. Receiver operating characteristic (ROC) curves were plotted to estimate the diagnostic value in CRC. Relationship between serum Linc01836 expression and clinicopathological characteristics of CRC cases was analyzed via chi-square test. The underlying mechanism of Linc01836 on the development and prognosis in CRC was predicted by bioinformatic analysis. Results: The method of qRT-PCR for Linc01836 detection was confirmed with high precision and specificity. Serum Linc01836 expression in CRC patients was significantly higher than that in healthy donors (p < 0.0001) and benign patients (p < 0.0001), and declined after resection (p < 0.01). High expression of Linc01836 was associated with histological stage (p = 0.002) and lymph node metastasis (p = 0.006). In addition, serum Linc01836 could effectively differentiate CRC patients from the healthy folks, with favorable area under the curve (AUC) of 0.809 (95% CI: 0.757–0.861, p < 0.001). What is more, the combination of serum Linc01836, CEA, and Cyfra21-1 could improve diagnostic sensitivity (92.0%). Linc01836 was averagely located in the nucleus and cytoplasm, suggesting that it might participate in CRC progression and prognosis through the crosstalk among lncRNAs, miRNAs, and mRNAs. Conclusion: Linc01836 may serve as a valuable noninvasive biomarker for population screening, early detection, and clinical surveillance of CRC. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal miR-92a-3p could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal miR-92a-3p in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal miR-92a-3p in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal miR-92a-3p was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal miR-92a-3p, CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal miR-92a-3p could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long intergenic non-coding RNA (lincRNA) belongs to a special type of RNA that is unable to encode proteins but has been proved to play a role in gene regulation and differentially expressed in various malignant tumors. OBJECTIVE: In this study, we aimed to identify whether lincRNA LINC00173 was differentially expressed in non-small-cell lung cancer (NSCLC) and whether it could serve as a potential diagnostic biomarker. METHODS: The quantification real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00173 in serum and cultured cells. For large sample analysis, the lncRNA expression matrix in TCGA database were generated via R software. To evaluate the diagnostic performance of serum LINC00173, the receiver operating characteristic (ROC) curve was used. RESULTS: The qRT-PCR analysis showed that the serum LINC00173 expression level in 108 NSCLC patients was higher than that in 91 healthy donors and 55 patients with benign pulmonary disease (BPD). And the area under the curve (AUC) of serum LINC00173 was 0.809 for the diagnosis of NSCLC (95% CI: 0.750–0.868, p < 0.001), 0.670 for BPD (95% CI: 0.584–0.756, P < 0.001), and 0.730 for small-cell lung cancer (SCLC, 95% CI: 0.636–0.825, P < 0.001). Besides, we established a diagnostic model of combined detection of LINC00173, CEA and Cyfra21-1, and found that combined detection of these indicators significantly improved the diagnostic efficiency. Analysis of the Clinicopathological parameters showed that high LINC00173 expression was correlated with histological typing of tumor, tumor metastasis and serum Cyfra21-1 levels. In addition, serum LINC00173 expression decreased in patients who received chemotherapy and rebound in recurrent NSCLC patients. CONCLUSION: Serum LINC00173 may prove to be a potential non-invasive auxiliary diagnostic biomarker for NSCLC patients. [ABSTRACT FROM AUTHOR]

Loss of one or some specific miRNA‐mediated regulation is closely associated with malignant progression of multiple myeloma (MM). But how these miRNAs work and what role the specific miRNA plays in this process of malignant progression remain unclear. It was found in this study that the expression of miR‐129 was decreased in both MM cell lines and newly diagnosed MM patients. Further clinicopathological statistics showed that miR‐129 was correlated with the isotype of MM patients. MiR‐129 overexpression disturbed cell proliferation, cell cycle evolution and spurred apoptosis both in vitro and in vivo. MAP3K7, a kinase able to activate NF‐κB circuit, was found to be up‐regulated in MM and contain a binding target of miR‐129. In addition, lncRNA PCAT‐1 functioned to sponge miR‐129 and thereby lowered its expression. PCAT‐1 knockdown eliminated the tumour‐promoting effect caused by miR‐129 inhibition, probably through repressing MAP3K7 and subsequent NF‐κB activation. To the best of our knowledge, this is the first study to have discovered that increased expression of PCAT‐1 could augment cell proliferation and cycle procession and inhibit apoptosis by down‐regulating miR‐129 via the MAP3K7/NF‐κB pathway in MM. [ABSTRACT FROM AUTHOR]

Digestive system cancer remains a common cancer and the main cause of cancer‐related death worldwide. Drug resistance is a major challenge in the therapy of digestive system cancer, and represents a primary obstacle in the treatment of cancer by restricting the efficiency of both traditional chemotherapy and biological therapies. Existing studies indicate that noncoding RNAs play an important role in the evolution and progression of drug resistance in digestive system cancer, mainly by modulating drug transporter‐related proteins, DNA damage repair, cell‐cycle‐related proteins, cell apoptosis‐related proteins, drug target‐related proteins, and the tumor microenvironment. In this review, we address the potential mechanisms of ncRNAs underlying drug resistance in digestive system tumors and discuss the possible application of ncRNAs against drug resistance in digestive system tumors. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a hematologic malignancy characterized by unrestricted secretion of monoclonal immunoglobulin and uncontrolled plasma cell proliferation. Extra‐medullary infiltration and drug resistance are two major obstacles in the treatment of MM. To solve these problems, it is necessary to elucidate the underlying pathological mechanisms and find new therapeutic targets. Noncoding RNAs (ncRNAs), which were once considered "transcriptional noise," have been recognized as crucial regulators in the process of tumorigenesis including MM. Increasing evidence has shown that ncRNAs participate in MM pathogenesis via a series of complex cellular or extracellular processes. This review article summarizes examples of ncRNAs involved in myelosis and discusses their potential as biomarkers and therapeutic targets in the diagnosis and treatment of myelosis. Noncoding RNAs (ncRNAs), which were once considered "transcriptional noise," have been recognized as crucial regulators in the process of tumorigenesis including multiple myeloma (MM). Increasing evidence has shown that ncRNAs participate in MM pathogenesis via a series of complex cellular or extracellular processes. This review article summarizes examples of ncRNAs involved in myelosis and discusses their potential as biomarkers and therapeutic targets in the diagnosis and treatment of myelosis. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a common hematological malignancy that is often associated with osteolytic lesions, anemia and renal impairment. Deregulation of miRNA has been implicated in the pathogenesis of MM. It was found in our study that miR-19b and miR-20a as members of crucial oncogene miR-17-92 cluster were differentially expressed between patients with MM and normal controls by genechip microarray, and this result was further confirmed in sera of patients with MM by qRT-PCR. The functional effect of miR-19b/20a was analyzed and results showed that miR-19b/20a promoted cell proliferation and migration, inhibited cell apoptosis and altered cell cycle in MM cells. PTEN protein expression was reduced after transfection of miR-19b/20a, suggesting that PTEN was a direct target of miR-19b/20a. In addition, over-expression of miR-19b/20a reversed the anti-proliferation and pro-apoptosis effect of PTEN in MM cells. Finally, our in vivo experiment demonstrated that lentivirus-mediated delivery of miR-20a promoted tumor growth in murine xenograft model of MM, which provide evidence that miR-20a inhibitor exerts therapeutic activity in preclinical models and supports a framework for the development of miR-19b/20a-based treatment strategies for MM patients. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common types of malignant neoplasm in women; the incidence of BC increases yearly. In a previous study, a novel and sensitive method for quantitying cell-free DNA (CFD) in human blood was established and tested for its ability to predict which patients harbored tumors. Our objective in this study was to investigate the clinical value of serum concentration and the integrity of circulating free DNA (CFD) as a biomarker for auxiliary diagnosis of BC. The concentration of CFD was quantitated by branched DNA (bDNA)–based Alu assay. Carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) concentrations were determined via Abbott ARCHITECT I2000 SR testing. We report that the median (quartile interval) values of serum ALU115 and ALU247/115 in patients with BC were significantly higher than those in patients with benign mammary hyperplasia and in healthy control individuals (1083.66 ng/mL [1.81] vs 145.87 ng/mL [0.33] and 228.19 ng/mL [0.48]; P <.001); there was no significant difference between the latter 2 groups (P >.05). The cutoff values of ALU115, ALU247/115, CEA, and CA15-3 were set as 300.96 ng per mL, 0.78, 5 ng per mL, and 31.3 ng per mL, respectively. The area under the receiver operating characteristic (ROC) curve was 0.70 (95% confidence interval [CI], 0.58–0.81), 0.97 (<.001–>.99), 0.75 (0.65–0.86), and 0.89 (0.82–0.96), respectively. Combined detection of the 4 indices significantly improved the diagnostic accuracy of BC, with sensitivity of 97.5% and negative predictive value of 96.4%. Also, serum ALU115 was significantly correlated with lymph-node metastasis (P =.048), and the ALU247/115 index was significantly correlated with tumor stage (P =.001) and lymph-node metastasis (P =.008) in patients with BC. Serum cell-free DNA (CFD) and its integrity may prove to be useful biomarkers for auxiliary diagnosis, grading of malignant neoplasms, and prognostic prediction of BC. [ABSTRACT FROM AUTHOR]

Objectives To explore microRNA-574-3p expression in serum of patients with hepatocellular carcinoma and investigate correlations between serum microRNA-574-3p expression and the development and prognosis of hepatocellular carcinoma. Design and methods Serum samples were collected from 70 patients with primary hepatocellular carcinoma, 40 patients with cirrhosis and 45 healthy controls. Serum microRNA-574-3p expression levels were detected by real-time quantitative polymerase chain reaction. The linearity, specificity and reproducibility were evaluated. In addition, the diagnostic value of microRNA-574-3p and its correlations with clinicopathologic features were assessed. Results The relative expression of microRNA-574-3p in hepatocellular carcinoma patients, cirrhosis patients and healthy controls was 2.306 (1.801-3.130), 1.362 (0.994-1.665) and 1.263 (0.765-1.723), respectively, indicating that it was significantly higher in hepatocellular carcinoma patients than that in the other two groups ( U = 439.5, 514.5, both P < 0.0001) and was significantly correlated with hepatitis B virus DNA copies ( U = 383.0, P = 0.018). In hepatitis B virus-positive hepatocellular carcinoma patients, the relative expression of microRNA-574-3p was significantly correlated with hepatitis B virus DNA concentration ( r = 0.348, P = 0.022). Compared with healthy control group, AUCROC of serum microRNA-574-3p in hepatocellular carcinoma group was 0.837 with 95% CI: 0.763-0.910. Combining microRNA-574-3p, AFU and alpha-fetoprotein together, the sensitivity was highest compared with other markers alone or combined. Conclusions The relative expression of serum microRNA-574-3p in hepatocellular carcinoma patients was significantly higher than that in cirrhosis patients and healthy controls, and it may be an important biomarker in the auxiliary diagnosis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM), accounting for ∼1% of all types of human cancer and 13% of all hematological malignancies, is characterized by the malignant proliferation of monoclonal plasma cells (PCs) in the bone marrow. MM leads to end stage organ impairment, including bone lesions, renal dysfunction, hypercalcemia and anemia. So far, the specific pathogenesis of MM remains unclear and no early-stage sensitive biomarker of MM has been well characterized. Furthermore, treating MM is difficult, as the majority of patients eventually relapse or become refractory following treatment using presently available methods. To date, a number of studies have demonstrated that microRNAs (miRNAs) may serve crucial functions in the progression of numerous cancers, including MM. During the tumorigenesis and pathogenesis of MM, there are multiple carcinogenic events that involve the pernicious transformation from normal to malignant PCs. miRNAs, as oncogenes or tumor suppressors, regulate MM progression-related signaling pathways. In the present review, the up-to-date preliminary basic studies and associated clinical works on the underlying mechanisms of aberrant miRNA profiling in MM have been summarized, including an evaluation of its value as a potential biomarker and a novel therapeutic strategy for MM. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to explore serum miR-135a-5p expression in colorectal cancer and examine the potential usefulness of this molecule as a biomarker for diagnosis in colorectal cancer. Methods Serum samples were collected from 60 patients with primary colorectal cancer, 40 patients with colorectal polyps and 50 healthy controls. Serum miR-135a-5p expression levels were detected by reverse transcription quantitative real-time quantitative polymerase chain reaction. Serum carcinoembryonic antigen and carbohydrate antigen 199 concentrations were detected by MODULAR ANALYTICS E170. Results The relative expression level of serum miR-135a-5p in colorectal cancer patients, colorectal polyps patients and healthy controls was 2.451 (1.107, 4.413), 0.946 (0.401, 1.942) and 0.949 (0.194, 1.415), respectively, indicating that it was significantly higher in colorectal cancer patients than that in the other two groups ( U = 351.0, 313.0, both P < 0.001). Additionally, it was significantly correlated with different degrees of tumour differentiation ( U = 215.0, P = 0.029) and different tumour stages ( U = 202.0, P = 0.013). There was no significant correlation between the relative expression of serum miR-135a-5p and carcinoembryonic antigen ( r2 = 0.023, P = 0.293) or carbohydrate antigen 199 ( r2 = 0.067, P = 0.068) in colorectal cancer patients. Compared with colorectal polyps group, AUCROC of serum miR-135a-5p in colorectal cancer group was 0.832 with 95% CI 0.73-0.93; compared with healthy control group, AUCROC was 0.875 with 95% CI 0.80-0.95. Conclusion Serum miR-135a-5p expression in colorectal cancer patients was higher than that in patients with colorectal polyps and healthy controls, suggesting that serum miR-135a-5p may prove to be an important biomarker for auxiliary diagnosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

The article discusses the clinical significance of miRNA-202 (miR-202) expression in multiple myeloma patients' serum. Correlations between serum miR-202 expression and the development and prognosis of multiple myeloma (MM) are investigated. Researchers extracted RNA from serum using miRNeasy Mini kit and performed the reverse transcription with specific stem-loop primers. It notes that researchers found higher expression of miR-202 in MM patients in comparison to healthy controls.

Emerging evidence indicates that exosomes can be used as a potential biomarker for monitoring diseases, including cancer. However, enhancing the sensing performance in terms of convenience and sensitivity remains an urgent demand for exosomes detection. In this study, a pH-sensitive colorimetric biosensing strategy was developed for exosomes detection by integrating stimuli-responsive DNA microcapsules and acetylcholinesterase to produce acetic acid. The constructed DNA microcapsules consisted of DNA shells crosslinked by anti-CD63 aptamers and loaded with acetylcholinesterase. With exosomes addition, an energetically stabilized aptamer-CD63 compound was produced and microcapsules dissociated due to the reaction of surface protein CD63 of exosomes and aptamer of CD63, resulting in the release of encapsulated AChE. Through a simple centrifugation separation, unreacted DNA microcapsules were removed and the supernatant containing released acetylcholinesterase collected, which was then used for colorimetric exosomes detection through the ability of acetylcholinesterase to hydrolyze acetylcholine to release acetic acid. The resulting decreased solution pH was detected with phenol red indicator, with the sharp color transition conveniently by naked eye. Exosomes quantification was also achieved using the solution's absorption intensity ratio of 558 vs. 432 nm. The linear range was from 2.0 × 103 to 5.0 × 105 particles/μL, and the limit of detection and limit of quantification were 1.2 × 103 particles/μL and 2.2 × 103 particles/μL, respectively. In addition, this proposed strategy for exosomes detection showed a relative standard deviation of 3.1% and high recovery efficiency (>94%), exhibiting a bright application future in exsomes analysis. A pH-sensitive colorimetric biosensing strategy was explored for exosomes detection by integrating the stimuli-responsive DNA microcapsules and acetylcholinesterase to produce acetic acid. [Display omitted] • A pH-responsive colorimetric strategy was fabricated for exosomes detection. • The convenient signal readout by naked-eyes with phenol red as the indicator. • Exosomes triggered the releasing of encapsulated acetylcholinesterase from DNA microcapsules. • The large inner space of DNA microcapsules produced an amplification effect. • The proposed strategy can be extended as a general analytical platform. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC. Methods: Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein–protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC. Results: A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone‐mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC. Conclusion: Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNAs) are functional RNA segments longer than 200 nucleotides, which are considered a redundant transcriptional product. Recently, lncRNAs have been shown to harbor open reading frame (ORF) sequences and encode proteins/peptides. Circular RNAs (circRNAs) have long been considered as another type of non-coding RNA (ncRNA) due to the absence of the 5′ cap structure. However, recent studies have shown that they also have ORFs in their sequences. CircRNAs can be translated into proteins via internal ribosome entry site (IRES)-driven or N6-methyladenosine (m6A)-mediated initiation. To date, several translatable circRNAs and lncRNAs have been identified in Drosophila, mice, and human myoblasts, as well as in different cancers, such as glioma, hepatocellular carcinoma, and colon cancer. In this article, we review the mechanisms that drive translation of circRNAs and lncRNAs. Moreover, we discuss the research methods and tools available to identify their translation products and validate the function of these bioactive proteins/peptides in physiology and cancer. • CircRNAs and lncRNAs have long been considered not translatable and non-coding. • Discovery of IRES and sORFs and characterization of m6A have challenged this view. • CircRNAs and lncRNAs are translated into proteins/peptides with diverse functions. • We review circ/lncRNA translation-driving mechanisms and role of their products. [ABSTRACT FROM AUTHOR]

Circulating long noncoding RNA (lncRNA) H19 has been reported to be a biomarker for cancer monitoring. The purpose of this study was to determine whether serum lncRNA could serve as a novel biomarker for the diagnosis of multiple myeloma (MM) and evaluate its value of clinical application. In our study, the expression of lncRNA H19 was up-regulated in 80 patients with MM and MM cell lines by RT-PCR analysis. Clinicopathological analysis showed the expression level of H19 could assist clinical staging, and the severity of the disease could be roughly determined according to the amount of H19 expressed in the patient serum. This is the first report to show that H19 was expressed in the serum of MM patients, suggesting that upregulation of serum lncRNA H19 may prove to be a novel biomarker for early diagnosis and clinical treatment of MM. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the expression levels of CD31+CD54+ and CD31+CD105+ endothelial microparticles (EMPs) before and after intravenous immunoglobulin (IVIG) treatment of Kawasaki disease (KD). To explore the role of human umbilical cord mesenchymal stem cells (hucMSCs) in inhibiting endothelial inflammation in KD, the effects of hucMSCs on the expression of CD54 and CD105 in endothelial cells in KD were analyzed in vivo and in vitro. The concentrations of IL-1β and VEGF in the peripheral blood of KD or healthy children were detected, and the distributions of CD31+CD54+ and CD31+CD105+ EMPs in platelet-poor plasma (PPP) were analyzed by flow cytometry. Human umbilical vein endothelial cells (HUVECs) were first cocultured with the patients' peripheral blood mononuclear cells (PBMCs). Next, HUVECs were cocultured with hucMSCs after stimulation with inactivated serum from patients. Cell proliferation and migration activities were assessed, and the expression of CD54, CD105 and IL-1β was analyzed. In an in vivo study, hucMSCs were transplanted into KD mice. The locations and expression levels of CD54, CD105 and IL-1β in the heart tissues of mice were analyzed. The levels of IL-1β and CD31+CD54+ EMPs were significantly higher before IVIG treatment and 2 weeks after treatment in KD patients (P < 0.01). However, the levels of VEGF and CD31+CD105+ EMPs increased significantly in KD only after IVIG treatment (P < 0.01). KD-inactivated serum stimulation combined with cocultivation of PBMCs can activate inflammation in HUVECs, leading to reduced cell proliferation and migration activities. Cocultivation also increased the expression of CD54 and decreased the expression of CD105 (P < 0.001). Cocultivation with hucMSCs can reverse these changes. Additionally, hucMSC transplantation downregulated the expression of IL-1β and CD54 and significantly upregulated the expression of CD105 in KD mice. The expression levels of CD31+CD54+ and CD31+CD105+ EMPs showed inconsistent changes at different KD statuses, providing potential markers for clinical application. HucMSCs suppress inflammation and regulate the expression levels of CD54 and CD105 in vascular endothelial cells in KD, possibly providing a new basis for stem cell therapy for KD. • CD31+CD54+ and CD31+CD105+ EMPs change inconsistently at different stages of KD, potentially reflect endothelial function. • HucMSCs suppress inflammation and regulate the expression levels of CD54 and CD105 in vascular endothelial cells in KD. • HucMSCs inhibit coronary artery inflammation while also promoting the repair of damaged tissues in KD mice. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that two long non-coding RNAs (lncRNAs), FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) and Actin filament associated protein 1 antisenseRNA1 (AFAP1-AS1), are highly expressed in different cancers, including gastric cancer (GC). However, the expression pattern and clinical utility of these two lncRNAs are still unknown. Serum expression levels of FEZF1-AS1 andAFAP1-AS1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). CEA and CA19-9 were detected by ARCHITET I2000 SR. Analyses were all performed using SPSS software version 20.0 (SPSS Inc., Chicago, USA). P < 0.05 was considered statistically significant. Detection of serum FEZF1-AS1 and AFAP1-AS1 showed both of them were up-regulated in GC patients compared with the normal controls (p < 0.0001), and high serum expression levels were correlated with tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis. Besides, the area under the ROC curve (AUC) demonstrated the two lncRNAs had higher diagnostic utility than CEA and CA19-9. Furthermore, when combined the two lncRNAs as a model, it yielded an AUC of 0.866, and the combination of the model, CEA and CA19-9 could observably improve diagnostic sensitivity to 95.5 %. What's more, circulating FEZF1-AS1 and AFAP1-AS1 were significantly decreased after the GC patients underwent the operation (both p < 0.001). Our study indicated that serum FEZF1-AS1 and AFAP1-AS1 had better sensitivity and efficiency for the diagnosis of GC and the combination of the two lncRNAs might be used as a potential prognostic indicator in GC. [ABSTRACT FROM AUTHOR]

Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Gastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro experiments demonstrated that circHAS2 knockdown or the addition of hsa-miR-944 mimics inhibited the proliferation, migration, and invasion ability of GC cells and affected the epithelial-mesenchymal transition. In addition, hsa-miR-944 interacted with protein phosphatase, Mg 2+ /Mn 2+ -dependent 1E (PPM1E), and was found to be a target gene of circHAS2. The upregulation of PPM1E reversed the effects of circHAS2 knockout on GC cells. The circHAS2/hsa-miR-944/PPM1E axis may be involved in the progression of GC; thus, circHAS2 may be a potential biomarker and therapeutic target for GC., (© 2021. The Author(s).)

Despite the continuous improvement of various therapeutic techniques, the overall prognosis of tumors has been significantly improved, but malignant tumors in the middle and advanced stages still cannot be completely cured. It is now evident that cell adhesion-mediated resistance (CAM-DR) limits the success of cancer therapies and is a great obstacle to overcome in the clinic. The interactions between tumor cells and extracellular matrix (ECM) molecules or adjacent cells may play a significant role in initiating the intracellular signaling pathways that are associated with cell proliferation, survival upon binding to their ligands. Recent studies illustrate that these adhesion-related factors may contribute to the survival of cancer cells after chemotherapeutic therapy, advantageous to resistant cells to proliferate and develop multiple mechanisms of drug resistance. In this review, we focus on the molecular basis of these interactions and the main signal transduction pathways that are involved in the enhancement of the cancer cells' survival. Furthermore, therapies targeting interactions between cancer cells and their environment to enhance drug response or prevent the emergence of drug resistance will also be discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Wang, Tang, Qin, Shen, He and Ju.)

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal miR-92a-3p could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal miR-92a-3p in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal miR-92a-3p in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal miR-92a-3p was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal miR-92a-3p , CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal miR-92a-3p could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC.

Exosomes are a group of nano-sized membrane vesicles and are important mediators of intercellular communication, particularly in tumor microenvironment. Recently, researchers have found that circular RNAs (circRNAs), with the great research significance, are enriched and stable in exosomes. In this review, we summarize the research significance of exosomal circRNAs, sorting mechanisms and their functioning mechanisms in tumor progression. Their clinical applications as clinical tumor biomarkers and as therapeutic targets in inhibiting tumor metastasis, anti-cancer immunity response and drug resistance have been widely discussed., (Copyright © 2020 Xu, Kong, Qin, Shen and Ju.)

Studies have shown that long non-coding RNAs (lncRNAs) play vital roles in the development of cancer, including colorectal cancer (CRC). Our purpose is to validate the diagnostic value of serum differentiation antagonizing non-protein coding RNA (DANCR) in CRC by focusing on its expression and clinical application. lncRNA expression profiles of CRC patients were obtained and analyzed by repurposing the publically available microarray data. Tissue or serum specimens were obtained from 40 patients with primary CRC, 10 patients with recurrent CRC, 40 patients with colorectal polyps, and 40 healthy controls. It was found that DANCR level in the CRC tissue and serum was significantly increased, and serum DANCR expression was decreased in post-operative patients as compared with that in pre-treatment patients and recurrent patients. In addition, serum DANCR expression was significantly correlated with different TNM stages. Correlation analysis of DANCR and other diagnostic indicators showed that the serum DANCR expression level was significantly correlated with CA199 but not with CEA in CRC patients. As for diagnostic efficiency by ROC analysis, the area under the curve (AUC) of serum DANCR was higher than that of CEA and CA199 in CRC group vs. colorectal polyp group. Simultaneous detection of DANCR, CEA and CA199 yielded the highest sensitivity and AUC as compared with either of them alone. Taken together, serum DANCR was up-regulated in CRC patients and high expression of DANCR may prove to be a potential biomarker for the diagnosis of CRC., (© 2020 The Author(s).)

Objective: Both previous and recent literature showed long non-coding RNAs (lncRNAs) were crucial participants in multiple myeloma (MM) evolution. However, the dynamic regulation and mechanism of lncRNAs in MM progression was not fully understood. This study will explore the expression and effects of prostate cancer-associated ncRNA transcript 1 (PCAT-1) in MM. Materials and Methods: The expression level of PCAT-1 was examined using quantitative real-time PCR in patients with newly diagnosed MM and cell lines. The potential biological effects and molecular mechanisms of PCAT-1 in MM were evaluated using a series of soft agar colony formation assay, CCK-8 assay, cell cycle and apoptosis assay by flow cytometry, protein chip arrays, western blot analysis, immunohistochemistry and nude subcutaneous tumorigenesis model. Results: High expression of PCAT-1 was observed in patients with newly diagnosed MM and cell lines. Over-expressed PCAT-1 enhanced cell division and inhibited apoptosis both in cultured cells and in animal model. Meanwhile, silenced PCAT-1 exerted the opposite function. Additionally, PCAT-1 knockdown sensitized MM cells to bortezomib (Bort). Inhibitor of PCAT-1 combination with Bort exhibited a more effective inhibitory effect on MM cells compared with negative control or Bort alone. Further mechanism exploration via protein chips, Go and KEGG pathway analysis along with immunoblot analysis revealed that PCAT-1 facilitated cell growth and drug resistance via the p38 and JNK MAPK pathways. Conclusion: This study identified a novel lncRNA-associated mechanism underlying MM carcinogenesis, and provided clinicians with a promising therapeutic target in MM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The morbidity and mortality of gastric cancer (GC) remain high worldwide. With the advent of the Human Genome Sequencing Project, circular RNAs (circRNAs) have attracted widespread attention in cancer research due to their stable ring structure. Our aim was to identify differentially expressed circRNAs in GC and explore their potential roles in GC diagnosis, treatment, and prognostic prediction. Methods: Large-scale gene screening was performed in three pairs of GC tissues and adjacent noncancerous tissues using high-throughput sequencing. The expression of hsa&#95;circ&#95;0001821 was detected in 80 pairs of tissue samples by quantitative real-time PCR (qRT-PCR). Stability of the ring structure of hsa&#95;circ&#95;0001821 RNA was verified by exonuclease digestion assay, and its diagnostic value was evaluated by receiver operating characteristic (ROC) analysis. In addition, the location of hsa&#95;circ&#95;0001821 in GC cells was detected by nucleoplasm separation assay. Results: A total of 25,303 circRNAs were identified, among which 2,007 circRNAs were differentially expressed (fold change > 2.0, P < 0.05). Further validation disclosed that hsa&#95;circ&#95;0001821 was significantly downregulated in the 80 pairs of GC tissues and 30 whole-blood specimens obtained from the GC patients. The specificity of hsa&#95;circ&#95;0001821 in GC was higher than that in other solid tumors. In addition, hsa&#95;circ&#95;0001821 was relatively stable after RNA exonuclease digestion. Clinicopathological parameter analysis showed that hsa&#95;circ&#95;0001821 was negatively correlated with tumor depth ( r = -0.255, P = 0.022) and lymph node metastasis ( r = -0.235, P = 0.036). Area under the curve (AUC) analysis showed that the diagnostic efficiency of circulating hsa&#95;circ&#95;0001821 in distinguishing GC patients was higher than that in GC tissues (0.872, 95%CI: 0.767-0.977 vs. 0.792, 95%CI: 0.723-0.861). Combined use of circulating hsa&#95;circ&#95;0001821 with the existing tumor markers yielded the largest AUC of 0.933. Finally, hsa&#95;circ&#95;0001821 was demonstrated to mainly locate in the cytoplasm, implying that it played a potential regulatory role in GC at the posttranscriptional level. Conclusion: Hsa&#95;circ&#95;0001821 may prove to be a new and promising potential biomarker for GC diagnosis., (Copyright © 2019 Kong, Yang, Tang, Wang, Shen and Ju.)

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors in the world, and non-coding RNA (ncRNA) has recently been widely reported to participate in the development of NSCLC. Some ncRNAs, especially microRNAs (miRNAs), are widely reported as tumor drug targets due to their short transcript length and easiness for processing into small molecule compounds. Therefore, exploring the potential roles of specific miRNAs in NSCLC may provide a better understanding of the molecular etiology. In this study, we downloaded the large-scale RNA-seq data from the Cancer Genome Atlas (TCGA) database, and identified 211 differentially expressed miRNAs (121 up-regulated and 90 down-regulated) in NSCLC. Similar to the TCGA database, miR-182-5p was significantly up-regulated in the serum and tissue samples of NSCLC patients. Clinicopathological parameters revealed the positive correlation between miR-182-5p expression and advanced TNM stage. Functional tests showed miR-182-5p overexpression promoted cell proliferation, migration and apoptosis inhibition, while miR-182-5p knockdown weakened the above phenotypes. Besides, advanced glycosylation end-product specific receptor (AGER) was identified as a direct downstream target of miR-182-5p. Alteration of AGER expression or NF-κB inhibitor could partially counteract the bioactive roles induced by miR-182-5p overexpression or knockdown. Further study disclosed down-regulated LINC00173 was negatively corrected with miR-182-5p in NSCLC tissues. LINC00173 could regulate miR-182-5p expression and reversed functional behaviors mediated by miR-182-5p/AGER/NF-κB axis. Taken together, miR-182-5p mediated the malignant phenotypes through NF-κB pathway via targeting AGER, and LINC00173 acted as a potential negative regulator of miR-182-5p in NSCLC cells., Competing Interests: None.

Autophagy is an important process in endogenous substrate degradation by lysosomes within cells, with a degree of evolutionary conservation. Like apoptosis and cell senescence, cell autophagy is a very important biological phenomenon involving the development and growth of biological processes. Abnormal autophagy may lead to tumorigenesis. In recent years, increasing studies have demonstrated that long non-coding RNAs (lncRNAs) and miRNAs can regulate cell autophagy by modulating targetting gene expression. In this review, we will provide an overview of lncRNAs and miRNAs in autophagy modulation and new insights into the underlying mechanisms, as well as their potential utilization in disease diagnosis, prognosis, and therapy., (© 2018 The Author(s).)

Background: miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer., Methods: We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR., Results: Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U=8, p=0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U=374, p<0.0001) and was significantly correlated with β2M, λ light and κ light chain concentration (r=0.480, p=0.0003; r=0.560, p<0.0001; r=0.560, p<0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r=0.247, p=0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826-0.945), which is higher than for other markers. Combining miR-4449, λ light chain, and β2M together, the sensitivity was highest compared with λ light chain or β2M alone, or combined., Conclusions: The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM.

Objective: The purpose of this study was to explore serum PCAT-1 expression in multiple myeloma (MM) and examine the potential usefulness of this molecule as a biomarker for diagnosis in MM., Methods: Serum samples were collected from 60 newly diagnosed untreated MM patients, and 48 healthy controls. Serum PCAT-1 expression levels were detected by RT-qPCR. In addition, correlations between the relative expression of serum PCAT-1 and the concentrations of lactic acid dehydrogenase (LDH), β2M, λ light chain and κ light chain were assessed., Results: It was found that the relative expression of serum PCAT-1 in MM patients (81.02 ± 136.9) was higher than that in healthy controls (3.17 ± 5.75) (U= 307.0, P< 0.0001) and was significantly correlated with β2M concentration (r= 0.461, P= 0.0002), but not with LDH, κ light and λ light chain concentration (r= 0.061, P= 0.641; r= 0.007, P= 0.956; r=-0.090, P= 0.499 respectively). Additionally, it was significantly correlated with different isotype of MM (H= 7.464, P= 0.024). The AUC of the ROC curve of serum PCAT-1 was 0.892 (95% CI 0.833-0.950), which was higher than other markers. Combining PCAT-1 and β2M together, the sensitivity was highest compared with other markers alone, or combined., Conclusion: The expression levels of serum PCAT-1 in MM patients were significantly higher than that in healthy controls, suggesting that it may be useful in the auxiliary diagnosis of MM.