Search

Background: MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR‐205‐5p in lung cancer progression and diagnosis. Materials and Methods: MiR‐205‐5p was detected by quantitative real‐time PCR. The effect of miR‐205‐5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR‐205‐5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. Results: The miR‐205‐5p was increased in lung cancer tissues. MiR‐205‐5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3′ untranslated region, miR‐205‐5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR‐205‐5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR‐205‐5p in the diagnosis of non‐small‐cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer. Conclusions: MiR‐205‐5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR‐205‐5p is a novel and valuable biomarker for lung cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have evaluated the significance of the microRNA‐10b (miR‐10b) in the development and progression of many cancers. Their findings revealed that increased expression of miR‐10b is associated with unfavorable prognosis in patients with cancer. Results: A total of 1,834 patients from 19 studies were included in this study. A significantly shorter overall survival was observed in patients with increased expression of miR‐10b (hazard ratio [HR] = 1.99, 95% confidence interval [CI]: 1.51–2.61). Statistical significance was also observed in subgroup meta‐analysis stratified by the cancer type, cutoff value, analysis type, and sample size. Also, patients with a high expression level of miR‐10b had a poorer disease‐free survival rate (HR = 1.18, 95% CI: 1.05–1.33). In addition, the pooled odds ratios (ORs) showed that increased miR‐10b was also associated with positive lymph node metastasis (OR = 2.09, 95% CI: 1.45–3.03), distant metastasis (OR = 2.40, 95% CI: 1.57–3.67), tumor size (OR = 3.86, 95% CI: 2.25–6.64), and poor clinical stage (OR = 5.02, 95% CI: 3.37–7.47). Materials and Methods: A systematic literature search was conducted on a number of electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Springer, Google Scholar, and Gene expression omnibus. We retrieved the relevant articles to examine the association between the miR‐10b expression levels and patients' prognosis. The meta‐analysis was conducted using the RevMan 5.2 software and Stata SE12.0 software. Conclusions: High miR‐10b expression was correlated with poor clinical outcome, which indicated the potential clinical use of miR‐10b as a molecular biomarker for cancer, particularly in assessing prognosis for patients with cancers. Further studies should be performed to verify the clinical utility of miR‐10b in human solid tumors. [ABSTRACT FROM AUTHOR]

Background: T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is exclusively expressed in antigen-presenting cells and involved in immune regulation. However, the role of TIM-4 expressed in tumour cells remains completely unknown.Methods: Immunohistochemistry staining was used to examine TIM-4 or Ki-67 expression in tumour tissues. Real-time PCR or RT-PCR was performed to detect TIM-4 mRNA expression. Lung cancer cell growth and proliferation were conducted by CCK-8 assay and EdU staining. Cell cycle progression was analysed by flow cytometry. The PCNA and cell cycle-related proteins were verified by western blot. Co-IP assay was used to identify the interaction of TIM-4 and integrin αvβ3. The efficacy of TIM-4 in vivo was evaluated using xenograft tumour model.Results: The expression of TIM-4 in non-small-cell lung cancer (NSCLC) tissues was significantly higher than that of the adjacent tissues. Enhanced TIM-4 expression was negatively correlated with histological differentiation of lung carcinoma and lifespan of patients. Overexpression of TIM-4 promoted lung cancer cell growth and proliferation, and upregulated the expression of PCNA, cyclin A, cyclin B1 and cyclin D1, accompanied by accumulation of lung cancer cells in S phase. Interestingly, Arg-Gly-Asp (RGD) motif mutation abolished the effect of TIM-4 on lung cancer cells, which was further verified by tumour xenografts in mice. Furthermore, we found that TIM-4 interacted with αvβ3 integrin through RGD motif.Conclusions: This finding suggests that TIM-4 might be a potential biomarker for NSCLC that promotes lung cancer progression by RGD motif. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma. [ABSTRACT FROM AUTHOR]

Purpose: Downregulation of miRNA expression has been identified as a novel feature of renal cell carcinoma (RCC). Recently, miR-129-2 is well known to be frequently reduced by DNA methylation and has anti-tumor effects in various tumors but so far not in RCC. The aim of this study was to investigate the clinical significance and the role of it in RCC. Methods: The expression levels of miR-129-3p and miR-129-5p, two mature products of miR-129-2, were determined by real-time quantitative reverse transcription PCR in 69 cases of paired different kidney tumors and normal tissues and clear cell RCC (ccRCC) cell lines. The roles of them in RCC cells were assessed by functional analyses. Protein expression was detected by Western blot. Results: miR-129-3p, but not miR-129-5p, was widely attenuated in human ccRCC, and chromophobe RCC. miR-129-3p could yield 73.5 % accuracy in discriminating ccRCCs from normal tissues. The relative miR-129-3p expression significantly differed between malignant and benign kidney tumors. Importantly, low miR-129-3p levels were associated with short disease-free and overall survival. Ectopic expression of miR-129-3p robustly impaired RCC cell migratory and invasive properties, but had no impact on cell viability and cell cycle distribution. Finally, miR-129-3p decreased multiple metastasis-related genes in RCC cells, including SOX4, phosphorylation of focal adhesion kinase and MMP-2/9 expression. Conclusions: miR-129-3p may act as a promising diagnostic biomarker for discriminating ccRCC from benign tumors and normal tissues and an independent prognostic biomarker in ccRCC. miR-129-3p may exert its anti-metastatic function through modulating multiple targets. [ABSTRACT FROM AUTHOR]

Abstract: Neuropilin-2(Nrp2), which is a nontyrosine kinase transmembrane glycoprotein, can promote angiogenesis and is a poor prognostic factor in some human cancers. In the present study, to explore the expression and potential function of Nrp2 in salivary adenoid cystic carcinoma (SACC), immunohistochemistry was used to examine the Nrp2 expression in 50 SACCs and 20 normal salivary gland tissues nearby SACCs. The result showed that immunoreactivity for Nrp2 was detected in 47 of 50 SACCs, and its expression level had significant correlations with microvessel density, tumor size, TMN clinical stage, vascular invasion, and metastasis (P <0.05) of SACCs. In addition, inhibition of Nrp2 function by the receptor–ligand interaction-blocking antibody decreased cell migration, invasion, and angiogenic promotion without influences on the cell proliferation of Acc-3 cells. Taken together, the expression of Nrp2 protein is significantly correlated with tumor progression and angiogenesis in SACCs. These results suggest that Nrp2 may be a potential therapeutic target for SACCs. [ABSTRACT FROM AUTHOR]

Objectives: MicroRNAs possess essential effects on gastric cancer (GC), whereas the underlying mechanisms have not been fully uncovered. The present work focused on investigating the role of miR-381-3p in GC cellular processes and the possible mechanisms. Materials and Methods: miR-381-3p levels within GC tissues and cells were measured through quantitative real-time polymerase chain reaction (qRT-PCR). This study measured cell proliferation, apoptosis, and metastasis through EdU, colony formation, flow cytometry, and Transwell assays separately. TargetScan was adopted to predict the miR-381-3p targets, whereas luciferase reporter assay was adopted for confirmation. Results: miR-381-3p levels were decreased, whereas fibroblast growth factor receptor-2 (FGFR2) expression was increased in GC. miR-381-3p upregulation inhibited proliferation, migration, and invasion and it promoted the apoptosis of GC cells. Further, FGFR2 overexpression partly reversed the miR-381-3p-mediated impacts on GC cellular processes. Conclusions: This study provides an experimental basis, suggesting the potential of using miR-381-3p as the novel marker for GC. Clinical Trial Registration number: 2020-05. [ABSTRACT FROM AUTHOR]

Abstract: We conducted this study to evaluate the expression of leptin and its receptor, OB-Rb in gastric cancer and their relationship to clinicopathological features, VEGF and HER-2 expression, as well as the prognostic value. One hundred and ten gastric cancer specimens were detected for leptin, OB-Rb, VEGF and HER-2 by immunohistochemistry (IHC), and 96 specimens of normal gastric mucosa served as the control. The expression level of leptin, OB-Rb and HER-2 in gastric tissues were significantly higher than normal tissues (49.1% vs. 34.0%, 60.9% vs. 46.0%, 19.1% vs. 8.0%, P <0.05). There was a correlation between the expression of leptin and HER-2, both of which were significantly associated with invasion depth, lymph node metastasis, AJCC stage and VEGF expression. However, there was no correlation between OB-Rb expression and all clinicopathological features. Cox regression analyses showed that age, tumor size, histological grade, serosa invasion, AJCC stage, chemotherapy, leptin and HER-2 overexpression were prognostic factors. The survival of patients with leptin positive expression was significantly poorer than those with negative expression (OS: 20.0months vs. 32.5months, FPS: 12.0months vs. 18.0months, P <0.01). Leptin, rather than OB-Rb, played an important role in the progression and angiogenesis of gastric cancer, and was a prognostic factor for poor outcome. [Copyright &y& Elsevier]