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Circular RNAs (circ RNAs) have been found to play an important role in cancer development. However, the role of circRAB3IP in osteosarcoma (OS) is unclear. In the present study, We found that circRAB3IP was highly expressed in OS tissues and OS cells. High levels of circRAB3IP was correlated with advanced TNM stage, distant metastasis. CircRAB3IP knockdown inhibited cell proliferation, migration, and invasion. Moreover, circRAB3IP directly binds to miR-580-3p. TWIST1 is directly targeted by miR-580-3p. We also demonstrated that circRAB3IP act as the sponge of miR-580-3p to promote TWIST1 expression. CircRAB3IP promotes OS cells proliferation, migration, and invasion through modulating miR-580-3p/TWIST1 axis. Moreover, circRAB3IP facilitated tumor formation in vivo. Our findings suggested that circRAB3IP acts as an oncogene in OS by regulating miR-580-3p/TWIST1 axis., Graphical abstract

Exosomal microRNAs (miRNAs) have great potentials as a novel biomarker to predict lung cancer. We applied a miRNA microarray to identify aberrantly expressed serum exosomal miRNAs as candidate biomarkers for patients with lung adenocarcinoma (LUAD). Compared with the normal control, 31 exosomal miRNAs were found to be upregulated and 29 exosomal miRNAs were downregulated in the serum of LUAD respectively. Then, 10 dysregulated exosomal miRNAs expression levels in serum were further validated via qRT-polymerase chain reaction. Notably, exosomal miR-7977 was highest expressed and miR-98-3p was lowest expressed in the patients with LUAD, and exosomal miR-7977 showed significant correlation with the N stage and TNM stage with patients with LUAD (P < .05). Receiver operating characteristic curve showed that the abundant level of exosomal miR-7977 may predict LUAD with an area of under the curve (AUC) of 0.787. In comparison with exosomal miR-7977, exosomal miR-98-3p had a smaller area (0.719). The combination of exosomal miR-7977 and miR-98-3p improved the AUC to 0.816. Furthermore, in vitro experiments revealed that inhibition of miR-7977 enhanced the proliferation, invasion, and inhibited apoptosis in A549 cells, the opposite results were performed by miR-7977 mimics. In conclusion, exosomal miR-7977 was identified as a novel biomarker for patients with LUAD and may play as a tumor suppressor in lung cancer.

This study aimed to identify differential circular RNA (circRNA) in the plasma exosomes of patients with lung adenocarcinoma (LUAD) using high-throughput sequencing. First, exosomes were isolated using an exosome isolation kit and confirmed by Western blotting, transmission electron microscopy, and NanoSight Assay. Subsequently, plasma circRNA expression profiles were screened by high-throughput sequencing and confirmed by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) and Sanger sequencing. Finally, the circRNA-miRNA-mRNA network was performed to forecast the potential function of circRNAs. The result of high-throughput sequencing data documented that 182 differentially expressed exosomal circRNAs in all were screened, which included 105 that were upregulated and 78 that were downregulated in LUAD patients plasma compared with controls. The four upregulated circRNAs including circ_0001492, circ_0001346, circ_0000690, and circ_0001439 were identical to the sequencing data by qRT-PCR, and their latent circRNA-miRNA-mRNA interactions were exhibited. Taken together, our study firstly revealed the altered exosomal circRNA expression from plasma samples in patients with LUAD and supports the need for exploring their potential as biomarkers and the pathological effects of lung cancer.

The cancer/testis antigen lactate dehydrogenase-C4 (LDHC) is a specific isoenzyme of the LDH family that regulates invasion and metastasis in some malignancies; however, little is known regarding its role in progression of lung adenocarcinoma (LUAD). Thus, we investigated LDHC expression by immunohistochemistry, and analyzed its clinical significance in 88 LUAD specimens. The role and molecular mechanisms subserving LDHC in cellular proliferation, migration, and invasion were explored both in vitro and in vivo. As a result, we found that high LDHC expression was significantly correlated with clinicopathological features of aggressive LUAD and a poor prognosis. Overexpression of LDHC induced LUAD cells to produce lactate and ATP, increased their metastatic and invasive potential—, and accelerated xenograft tumor growth. We further demonstrated that overexpression of LDHC affected the expression of cell proliferation-related proteins (cyclin D1 and c-Myc) and epithelial-mesenchymal transition (EMT)-related proteins (MMP-2, MMP-9, E-cadherin, Vimentin, Twist, Slug, and Snail) both in vitro and in vivo. Finally, excessive activation of LDHC enhanced the phosphorylation levels of AKT and GSK-3β, revealing activation of the PI3K/Akt/GSK-3β oncogenic-signaling pathways. Treatment with a PI3K inhibitor reversed the effects of LDHC overexpression by inhibiting cellular proliferation, migration, and invasion, with diminished levels of p-Akt and p-GSK3β. PI3K inhibition also reversed cell proliferation-related and EMT-related proteins in LDHC-overexpressing A549 cells. In conclusion, LDHC promotes proliferation, migration, invasion, and EMT in LUAD cells via activation of the PI3K/Akt/GSK-3β pathway.

BACKGROUND Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been predicted to play a critical role in various biological processes including tumorigenesis. However, the clinical significance of UCA1 in lung adenocarcinoma (LUAD) is still not understood in detail. The aim of this study was to assess the clinical significance of the UCA1 expression levels in LUAD based on publicly available data and to evaluate its potential signaling pathways. METHODS The RNA-sequencing (RNA-seq) dataset and clinical information of all LUAD patients were downloaded from The Cancer Genome Atlas (TCGA). Kaplan-Meier plot and log-rank test were performed for survival analysis; Cox proportional hazards regression model were used to assess the relative factors. Furthermore, Starbase, Cbioportal, and Multi Experiment Matrix starbases were used to identify UCA1-related genes in LUAD. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of UCA1-related genes were performed using DAVID. RESULTS The expression level of UCA1 in LUAD tissues (n = 468) was significantly increased compared with the adjacent non-tumor lung tissues (n = 52) (p < 0.0001). In addition, UCA1 level was significantly correlated with TNM stage and lymph node metastasis. Survival analysis showed that UCA1 over-expression was significantly associated with poor overall survival (OS) (p = 0.0098) and poor recurrence-free survival (RFS) (p = 0.0298) in LUAD patients. Multivariate analysis confirmed that high expression of lncRNA-UCA1 was an independent prognostic factor of poor OS (HR = 1.353, 95% CI: 1.005 - 1.822, p = 0.046). Finally, KEGG analysis for UCA1-related genes indicated that UCA1 might be enriched with the microRNAs in cancer, pathways in cancer, endocytosis, focal adhesion, and proteoglycans in cancer. CONCLUSIONS This study showed that UCA1 may be involved in lung carcinogenesis, which could act as a biomarker of prognosis and therapeutic target in LUAD patients.

Liangyuan Chen,1,2 Chunli Huang,2 Xiaojun Yang,3 Qiuqin Zhang,1 Falin Chen1,2 1Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Department of Clinical Laboratory, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Transfusion Medicine, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China Background: The peroxiredoxin (PRDX) protein family is involved in cancer cell invasion and metastasis, but its prognostic value in lung cancer remain elusive. Methods: In this report, we accessed the overall survival (OS) of each individual PRDX mRNA expression through the Kaplan–Meier plotter (KM plotter) database, in which updated gene expression data and survival information include a total of 1,926 lung cancer patients. Results: Our results indicated that PRDX1 and PRDX2 mRNA expressions were associated with improved OS in all lung cancer patients especially in lung adenocarcinoma patients, whereas PRDX5 and PRDX6 mRNA expressions were associated with poor OS in all lung cancer patients. In addition, the prognostic value of PRDXs in the different clinicopathological features according to smoking status, pathological grades, clinical stages, and chemotherapeutic treatment of lung cancer patients was further assessed in the KM plotter database by the multivariate cox regression analysis. Conclusion: Our finding will elucidate the prognostic role of PRDXs in lung cancer and might promote development of PRDX-targeted inhibitors for the treatment of lung cancer. Keywords: PRDX, expression, prognostic, KM plotter, smoking status, lung cancer

It has been well-established that AKT2 plays an important role in the development and progression of colon cancer; however, its precise function remains unclear. In the present study, we found that AKT2 can interact with and phosphorylate hexokinase 2 (HK2), the rate-limiting enzyme in glycolysis. Moreover, threonine phosphorylation dramatically increases its catalytic activity and enhances glycolysis. Mechanistically, AKT2 phosphorylation of HK2 at T473 was found to increase hexokinase activity and lactic acid production. A mutation in the AKT2 phosphorylation site of HK2 substantially reduced the stimulating effects of AKT2 on glycolysis, cellular apoptosis, invasion, tumorigenesis, and metastasis. In addition, AKT2 regulated NF-κB, HIF1Α, MMP2, and MMP9 via the phosphorylation of HK2 at the T473 site. Taken together, AKT2 increases the invasion, tumorigenesis, and metastasis of colon cancer cells in vitro and promotes lung metastasis in nude mice in vivo through the phosphorylation of the T473 site of HK2 by upregulating NF-κB, HIF1α, MMP2, and MMP9. In conclusion, our findings highlight a novel mechanism for the AKT2-HK2-NF-κB/HIF1α/MMP2/MMP9 axis in the regulation of colon cancer progression. Moreover, our results suggest that both AKT2 and HK2 may be potential targets for the treatment of colon cancer.

In this contribution, the azo dye (E)-1-(4-((4-(phenylamino)phenyl)diazenyl) phenyl)ethanone (DPA) was combined with reduced graphene oxide (RGO) for the electrochemical modification of a pencil graphite electrode (RGO/DPA/PGE) surface. A series of electrochemical measurements were used for the characterization of the modified electrode surfaces. At the modified electrode, nicotine was irreversibly reduced. An obvious increase was observed in the reductive peak current of nicotine at the modified electrode, indicating the capability of the RGO/DPA composite to increase the electron transfer rate. The current was found proportional to the nicotine concentration in a range of 31 to 1900 μM, and the limit of detection (LOD) was calculated as 7.6 μM.

Background This study sought to improve and evaluate a 2-hydroxyvaleric acid based staining method for detection of lactate dehydrogenase C4 (LDH-C4) activity in human spermatozoa. Methods A staining method for measuring sperm LDH-C4 activity with the substrate 2-hydroxyvaleric acid was improved. Expression level of LDH-C4 was assessed by Western blotting. The diagnostic performance was evaluated by plotting the receiver operating characteristic (ROC) curve. Results The positive products were black purple lumps concentrated in the neck segment of spermatozoa. Expression level of LDH-C4 was significantly reduced in the low activity infertile cases as compared to the matched contrasts. Decreased LDH-C4 level was significantly correlated with the declined enzyme activity (r = 0.702, p = 0.000). The ROC curve allowed for the discrimination between low and normal LDH-C4 activity cases with a sensitivity of 0.912 and specificity of 0.895, corresponding to an area under curve (AUC) of 0.941. Conclusions The improved method hallmarks a promising accuracy in evaluating sperm LDH-C4 activity. Down-regulated LDH-C4 level is a culprit for the decreased LDH-C4 activity in spermatozoa.

The fragile X mental retardation 1 (FMR1) gene contains a highly polymorphic trinucleotide (CGG) repeat and consists of various allelic forms. Traditionally, 55-200 repeats and over 200 CGG repeats have been highlighted to be associated with ovarian dysfunction and neuro-psychiatric risks. However, previous studies had paid little attention to the allelic forms of 5-55 CGG repeats. Herein, we sought to evaluate the pathological features of FMR1 allelic category with a range of 5-55 CGG repeats. We further classified the spectrum of CGG sizes (5-55 repeats) into three sub-groups as low numbers of CGG repeat (26 repeats), normal CGG count (26-34 repeats), and small CGG expansion (35-54 repeats). Our systematic review documented that low numbers of CGG repeat (26 repeats) revealed a close relationship with premature ovarian failure. Correspondingly, the meta-analysis showed that small CGG expansion, involving allelic sizes with 35-54 (n = 8, OR = 1.22, 95% CI: 0.75-2.00, P0.05) and 41-54 (n = 7, OR = 1.62, 95% CI: 1.14-2.30, P0.05), was both linked to the risk of ovarian dysfunction. Additionally, small CGG expansion exerts significant influence on male Parkinsonism cohorts (OR = 2.17, 95% CI: 1.50-3.14, P0.05), mental retardation, and repeat instability. Our data provide evidence that the CGG-repeat numbers below 26 or above 34 of FMR1 gene are also associated with disease risks and thus should be regarded as pathological genotypes for a routine test.

Background Recent studies have provided new insights into the diagnostic value of sperm DNA fragmentation (SDF) for male factor sterility. This study aimed to systematically evaluate the diagnostic accuracy of the SDF test for male infertility. Methods Eligible studies were retrieved by searching electronic databases. The quality of the studies was assessed on the basis of quality assessment for studies of diagnostic accuracy (QUADAS) criteria tool. The bivariate metaanalysis model was employed to summarize the diagnostic indices and plot the summary receiver operator characteristic (SROC) curve by using Meta-disc 1.4 software. Influence analysis, meta-regression, and publication bias assay were all conducted through Stata 12.0 software. Results Our bivariate random effect meta-analysis yielded an AUC (area under curve) value of 0.9211 with a sensitivity (95% confidence interval) of 0.80 (0.78 - 0.82) and specificity of 0.83 (0.80 - 0.86) for the use of the SDF test in differentiating infertile males from normal fertile controls. Moreover, our subgroup analysis suggested that SDF analysis with a single TUNEL test resulted in an AUC value of 0.9506, with a pooled sensitivity of 0.77 (0.74 - 0.80) and specificity of 0.91 (0.87 - 0.94), while SCD and Comet assays displayed a combined sensitivity of 0.77 (0.67 - 0.81) or 0.91 (0.88 - 0.94), and specificity of 0.84 (0.75 - 0.91) or 0.63 (0.54 - 0.70), accompanied by an AUC value of 0.8408 or 0.9473. Conclusions The SDF assay confers a relatively high diagnostic accuracy for infertility detection, among which the TUNEL based methodology seems to achieve higher accuracy than the SCD and Comet assays.

Background Bladder cancer (BCa) is the fifth most common cancer with significant morbidity and mortality. Recently, numerous studies demonstrated that microRNAs (miRNAs) are emerging as diagnostic biomarkers for BCa. However, the findings in these studies are inconsistent. To systematically assess the potential diagnostic value of miRNAs for BCa, a meta-analysis was performed in this study. Methods Relevant literature was researched in PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases up to September 1, 2014. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and area under the SROC curve (AUC) value were analyzed by the random-effects model, whose parameters reflected the overall diagnostic performance of miRNAs. Results Thirty studies from 10 individual publications, including 1019 BCa patients and 690 controls, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.80 (95% CI: 0.78 - 0.81), 0.74 (95% CI: 0.72 - 0.76), 3.22 (95% CI: 2.68 - 3.87), 0.26 (95% CI: 0.21 - 0.32), 15.20 (95% CI: 10.25 - 22.53) and 0.85, respectively, indicating a moderate diagnostic accuracy for BCa. Moreover, our subgroup analyses showed that analysis of multiple miRNAs (AUC, sensitivity, and specificity of 0.913, 0.86, and 0.80, respectively) yielded a higher diagnostic accuracy than of single miRNAs (AUC, sensitivity, and specificity of 0.84, 0.78, and 0.73, respectively) in BCa diagnosis. In addition, as biomarkers, miRNAs are more suitable for the diagnosis of non-muscle-invasive BCa (NMIBCa) with AUC of 0.84, sensitivity of 0.74, and specificity of 0.77 than muscle-invasive BCa (MIBCa) with AUC of 0.79, sensitivity of 0.73, and specificity of 0.73. Conclusions The present meta-analysis suggests that miRNAs are potential novel biomarkers for detection of BCa. However, further validation studies are still needed to confirm our findings.