Normalized TSH strategy can improve the initial assessment of thyroid nodules.

BACKGROUND: Serum thyrotropin (TSH) has been recommended for the initial assessment of patients with thyroid nodules to exclude functional thyroid nodules (FTN). However, the sensitivity of TSH is very low. The increased level of thyroid peroxidase antibody (TPOAb) is considered to be one of the reasons. OBJECTIVE: To investigate whether normalized TSH (nTSH) can improve diagnostic efficiency by removing TPOAb interference in the first evaluation of thyroid nodules compared with traditional TSH strategy. METHODS: Thyroid nodules were retrospectively analysed in 90 patients with FTN and 1038 patients with non-functioning thyroid nodules (non-FTN). The regression coefficient (ß) of TPOAb affecting the TSH levels was assessed in patients with thyroid nodules, and then, the nTSH level was calculated based on the following formula: nTSH = TSH-ß*TPOAb. We used nTSH levels to initially evaluate the thyroid nodules instead of the traditional TSH values and finally compared the results of the two strategies. RESULTS: The sensitivity, specificity, accuracy, positive prediction rate (PPV) and negative prediction rate (NPV) of nTSH for accessing FTN were 50.00%, 87.70%, 84.67%, 26.01% and 95.29%, respectively, which were better than the values of 48.90%, 78.70%, 76.33%, 16.60% and 94.67% associated with TSH, respectively (p < 0.001). CONCLUSION: Serum TPOAb testing is recommended for the first assessment of thyroid nodules. Normalized TSH levels can improve assessment efficiency compared to traditional TSH assessment, increase the specificity and reduce an unnecessary 99mTc-TS test.

CCL22 and CCL26 are potential biomarkers for predicting distant metastasis in thyroid carcinoma.

OBJECTIVES: Chemokines have been suggested to play significant roles in the progression of malignant cancers. This study aimed to identify the chemokines related to malignant progression in thyroid carcinoma. METHODS: The mRNA expression levels of 52 chemokines were compared between differentiated thyroid cancer (DTC) samples and normal thyroid tissues from The Cancer Genome Atlas database; survival analysis was then performed on the basis of differentially expressed chemokines. A retrospective study was conducted on the level of differentially expressed chemokines in 76 DTC patients. Functional pathway analysis was performed to explore chemokine-related regulatory mechanisms. RESULTS: We identified 20 chemokines with differentially expressed mRNA levels through publicly available data. High levels of CCL22 and CCL26 were found to be related with metastasis in clinical DTC samples. High levels of CCL22 were found to be significantly related to poor prognosis in DTC patients. Pathway analyses revealed that cytokines might affect cancer progression through cytokine-cytokine receptor and cytokine-interleukin interactions. CONCLUSIONS: CCL22 and CCL26 could serve as prognostic biomarkers in thyroid carcinoma.

Research on the Expression Level of Matrin-Type Zinc Finger Protein 4 Gene in T Cells of Thyroid Carcinoma Tissue.

In order to analyze the expression level of zinc finger matrin-type protein 4 (ZMAT4) gene in T cells of thyroid carcinoma (TC) tissue and its clinical significance to prognosis of patients based on bioinformatics and reverse transcription polymerase chain reaction (RT-PCR), 389 TC patients with ZMAT4 gene and its corresponding survival and prognosis are searched by the Cancer Genome Atlas database. The expression of ZMAT4 gene is compared between normal thyroid tissue and TC tissue by RT-PCR. The relationship between ZMAT4 expression levels and clinicopathological parameters and baseline data is analyzed. The experimental results show that the low expression of ZMAT4 gene has an important relationship with the development of thyroid cancer, and real-time monitoring of ZMAT4 gene in TC patients can effectively evaluate the prognosis of patients.

Widely Targeted Metabolomics Analysis of Soybean and Chickpea and Their Different Advantages and New Functional Compounds for Diabetes.

Soybean is widely used as a kind of bean for daily consumption. Chickpea is increasingly utilised because of its good healthcare function. At present, using chickpeas could have better results than soybeans in some areas. Previous studies of the two legumes focused on certain components and failed to fully reveal the differences between the two legumes. Thus, understanding the comprehensive similarities and differences between the two legumes is necessary to apply and develop these legumes effectively. In this study, we performed a UPLC-ESI-MS/MS-based widely targeted metabolomics analysis on two legumes. A total of 776 metabolites (including primary metabolites and secondary metabolites) were detected, which were divided into more than a dozen broad categories. The differential analysis of these metabolites showed that there were 480 metabolites with significant differences in relative contents between the two legumes. Compared with soybean, the expression of 374 metabolites of chickpea was down-regulated and that of 106 metabolites was up-regulated. The metabolic pathway analysis showed significant differences in the flavonoids biosynthesis, phenylpropanoid biosynthesis, linoleic acid metabolism and alkaloid biosynthesis between the two legumes. The advantages and applicability of the two kinds of legumes were confirmed through the analysis of anti-diabetic components. Moreover, some novel compounds (with contents higher than that of soybean) with hypoglycaemic activity were found in chickpea. This study provides an important reference for the in-depth study and comparative application of soybean and chickpea.

Recycling municipal solid waste incineration fly ash in super-lightweight aggregates by sintering with clay and using SiC as bloating agent.

Municipal solid waste incineration (MSWI) fly ash is classified as hazardous waste and requires proper treatments. Sintering of MSWI fly ash for the production of lightweight aggregate (LWA) is a promising treatment technology, while the dependence on natural bloating clay to produce high quality LWA has limited its wide application. In this study, by using SiC as a bloating agent, normal clay could be used to produce super-lightweight aggregate (bulk density <500 kg/m3) with MSWI fly ash. Effects of SiC addition amount, sintering temperature and duration on LWA performance were studied. The results showed that LWA with SiC addition of 0.1-0.5 wt% had significant expansion at sintering temperature of 1120 °C-1160 °C. The optimal conditions were 0.3 wt% SiC addition and sintering at 1120 °C for 30 min, and the bulk density could reach 212 kg/m3 with other properties meeting the LWA standard (GB/T 17431.1-2010). Further, the heavy metal leaching toxicity was significantly decreased after sintering and met the MSWI fly ash utilization standard (HJ 1134-2020). The X-ray diffraction results revealed the formation of a complex diopside-based phase after sintering. This study provides a new approach for recycling MSWI fly ash in LWA without dependence on specific clay resources, and makes this technology wider applicability.

Iodine-catalyzed oxidative annulation: facile synthesis of pyrazolooxepinopyrazolones via methyl azaarene sp3 C-H functionalization.

An iodine-catalyzed methyl azaarene sp3 C-H functionalization has been developed for the synthesis of a seven-membered O-heterocyclic architecture containing three different heterocyclic aromatic hydrocarbons. This method can be applied to a wide range of substituted methyl azaarenes and diverse 2,4-dihydro-3H-pyrazol-3-ones, and brings about the efficient preparation of 2,9-dihydrooxepino[2,3-c:6,5-c']dipyrazol-3(7H)-ones in high yields with the merits of low catalyst loading, good functional group tolerance and metal-free conditions.

Gut microbiota changes and its potential relations with thyroid carcinoma.

Introduction: Emerging evidence suggests that the essence of life is the ecological balance of the neural, endocrine, metabolic, microbial, and immune systems. Gut microbiota have been implicated as an important factor affecting thyroid homeostasis. Objectives: This study aims to explore the relationship between gut microbiota and the development of thyroid carcinoma. Methods: Stool samples were collected from 90 thyroid carcinoma patients (TCs) and 90 healthy controls (HCs). Microbiota were analyzed using 16S ribosomal RNA gene sequencing. A cross-sectional study of an exploratory cohort of 60 TCs and 60 HCs was conducted. The gut microbiota signature of TCs was established by LEfSe, stepwise logistic regression, lasso regression, and random forest model analysis. An independent cohort of 30 TCs and 30 HCs was used to validate the findings. Functional prediction was achieved using Tax4Fun and PICRUSt2. TC patients were subsequently divided into subgroups to analyze the relationship between microbiota and metastatic lymphadenopathy. Results: In the exploratory cohorts, TCs had reduced richness and diversity of gut microbiota compared to HCs. No significant difference was found between TCs and HCs on the phylum level, though 70% of TCs had increased levels of Proteobacteria-types based on dominant microbiota typing. A prediction model of 10 genera generated with LEfSe analysis and lasso regression distinguished TCs from HCs with areas under the curves of 0.809 and 0.746 in the exploration and validation cohorts respectively. Functional prediction suggested that the microbial changes observed in TCs resulted in a decline in aminoacyl-tRNA biosynthesis, homologous recombination, mismatch repair, DNA replication, and nucleotide excision repair. A four-genus microbial signature was able to distinguish TC patients with metastatic lymphadenopathy from those without metastatic lymphadenopathy. Conclusion: Our study shows that thyroid carcinoma patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and TC pathogenesis.

miR-31-5p/SOX4 Axis Affects Autophagy and Apoptosis of Chondrocytes by Regulating Extracellular Regulated Protein Kinase/Mechanical Target of Rapamycin Kinase Signalling.

BACKGROUND: Osteoarthritis (OA) is a common type of degenerative joint diseases that is regulated by a combination of complex intercellular signals and modulators, including non-coding RNAs. Mounting evidence suggests that miR-31-5p is physiologically involved in the regulation of chondrocytes, but the mechanism remains unclear. METHODS: Expression levels of miR-31-5p and SOX4 in OA cartilage tissues and in IL-1ß-stimulated chondrocytes were examined by quantification polymerase chain reaction (q-PCR) or immunohistochemistry assays. Cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Expression of LC3 was detected using immunofluorescence staining. Expressions of autophagy-related proteins and extracellular regulated protein kinase (ERK)/mechanical target of rapamycin kinase (mTORC1) signal-related proteins were measured by Western blot analysis. Molecular interaction was validated by dual luciferase reporter assay. RESULTS: Downregulation of miR-31-5p and upregulation of SOX4 were observed in both OA patients and OA chondrocytes. Mechanistic experiments revealed that miR-31-5p negatively modulated SOX4 expression by directly targeting its 3'- untranslated region. Moreover, overexpression of miR-31-5p suppressed the activation of mTORC1 in an ERK-dependent manner by inhibiting SOX4. Further functional experiments demonstrated that overexpressing miR-31-5p in OA chondrocytes markedly promoted its proliferation and autophagy while inhibiting apoptosis. However, these effects were abolished by overexpression of SOX4 or treatment with 3BDO, an mTOR activator. CONCLUSION: These results demonstrated that miR-31-5p enhanced survival and autophagy of OA chondrocytes through inactivation of mTORC1 via directly targeting SOX4, suggesting that miR-31-5p may play a protective role in OA progression.

Analysis of Genetic Alterations Related to DNA Methylation in Testicular Germ Cell Tumors Based on Data Mining.

Embryonal carcinoma (EC) and seminoma (SE) are both derived from germ cell neoplasia in situ but show big differences in growth patterns and clinical prognosis. Epigenetic regulation may play an important role in the development of EC and SE. This study investigated the DNA methylation-based genetic alterations between EC and SE by analyzing the datasets of mRNA expression and DNA methylation profiling. The datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified between EC and SE by limma package in R environment. Gene function enrichment analysis of the DEGs was performed on the DAVID tool, the results of which suggested differences in capability of pluripotency and genomic stability between EC and SE. The minfi package and wANNOVAR tool were used to identify differentially methylated genes. A total of 37 genes were discovered with both mRNA expression and the accordant DNA methylation changes. The findings were verified by the sequencing data from The Cancer Genome Atlas database, and Kaplan-Meier survival analysis was performed. Finally, 5 genes (PRDM1, LMO2, FAM53B, HCN4, and FAM124B) were found that showed both low expression and high methylation in EC, and were significantly associated with relapse-free survival. The findings of methylation-based genetic features between EC and SE might be helpful in studying the role of DNA methylation in cancer development.

Dexmedetomidine Exerts Renal Protective Effect by Regulating the PGC-1α/STAT1/IRF-1 Axis.

BACKGROUND: Ischemia-reperfusion (I/R) injury is the main cause of acute kidney injury (AKI), and its incidence and mortality increase year by year in the population. Dexmedetomidine (DEX) can improve AKI by regulating inflammation and oxidative stress, but its mechanism is still unclear. METHODS: A hypoxia/reoxygenation (H/R) model of HK-2 cells and a kidney I/R model of C57BL/6J mice were established. In the experiment, cells were transfected with sh-PGC-1α to inhibit PGC-1α expression. The changes of ROS level and mitochondrial membrane potential (MMP) were analyzed. HE staining was used to assess kidney damage in mice. Concentration of kidney injury markers serum creatinine and blood urea nitrogen and expression of inflammatory factors were detected by ELISA. qPCR analysis was used to detect mRNA levels of related proteins in cells and mouse kidney tissues. The protein intracellular content and phosphorylation levels were determined by Western blotting. RESULT: The production of inflammatory factors and ROS was increased in HK-2 cells treated with H/R, while MMP, cell viability, and mitochondrial-related protein levels were decreased. DEX attenuated pathological changes induced by H/R, while knockdown of PGC-1α eliminated the mitigation effect. DEX inhibited the damage of I/R to the kidneys of mice and increased the expression of mitochondrial-related proteins and PGC-1α in the kidneys, while inhibiting the phosphorylation of STAT1 and the expression of IRF-1. CONCLUSIONS: DEX appears to inhibit mitochondrial damage and cellular inflammation by upregulating PGC-1α to affect STAT1 phosphorylation level and IRF-1 expression, thereby preventing AKI.

Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease.

Background: Gut microbiota are considered to be intrinsic regulators of thyroid autoimmunity. We designed a cross-sectional study to examine the makeup and metabolic function of microbiota in Graves' disease (GD) patients, with the ultimate aim of offering new perspectives on the diagnosis and treatment of GD. Methods: The 16S ribosomal RNA (rRNA) V3-V4 DNA regions of microbiota were obtained from fecal samples collected from 45 GD patients and 59 controls. Microbial differences between the two groups were subsequently analyzed based on high-throughput sequencing. Results: Compared with controls, GD patients had reduced alpha diversity (p < 0.05). At the phylum level, GD patients had a significantly lower proportion of Firmicutes (p = 0.008) and a significantly higher proportion of Bacteroidetes (p = 0.002) compared with the controls. At the genus level, GD patients had greater numbers of Bacteroides and Lactobacillus, although fewer Blautia, [Eubacterium]_hallii_group, Anaerostipes, Collinsella, Dorea, unclassified_f_Peptostreptococcaceae, and [Ruminococcus]_torques_group than controls (all p < 0.05). Subgroup analysis of GD patients revealed that Lactobacillus may play a key role in the pathogenesis of autoimmune thyroid diseases. Nine distinct genera showed significant correlations with certain thyroid function tests. Functional prediction revealed that Blautia may be an important microbe in certain metabolic pathways that occur in the hyperthyroid state. In addition, linear discriminant analysis (LDA) and effect size (LEfSe) analysis showed that there were significant differences in the levels of 18 genera between GD patients and controls (LDA >3.0, all p < 0.05). A diagnostic model using the top nine genera had an area under the curve of 0.8109 [confidence interval: 0.7274-0.8945]. Conclusions: Intestinal microbiota are different in GD patients. The microbiota we identified offer an alternative noninvasive diagnostic methodology for GD. Microbiota may also play a role in thyroid autoimmunity, and future research is needed to further elucidate the role.

The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion.

The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3'-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107-meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.

Anti-Apoptotic Effects of Docosahexaenoic Acid in IL-1ß-Induced Human Chondrosarcoma Cell Death through Involvement of the MAPK Signaling Pathway.

Osteoarthritis (OA) is a degenerative disease characterized by progressive articular cartilage destruction and joint marginal osteophyte formation with different degrees of synovitis. Docosahexaenoic acid (DHA) is an unsaturated fatty acid with anti-inflammatory, antioxidant, and antiapoptotic functions. In this study, the human chondrosarcoma cell line SW1353 was cultured in vitro, and an OA cell model was constructed with inflammatory factor IL-1ß stimulation. After cells were treated with DHA, cell apoptosis was measured. Western blot assay was used to detect protein expression of apoptosis-related factors (Bax, Bcl-2, and cleaved caspase-3) and mitogen-activated protein kinase (MAPK) signaling pathway family members, including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38 MAPK. Our results show that IL-1ß promotes the apoptosis of SW1353 cells, increases the expression of Bax and cleaved caspase-3, and activates the MAPK signaling pathway. In contrast, DHA inhibits the expression of IL-1ß, inhibits IL-1ß-induced cell apoptosis, and has a certain inhibitory effect on the activation of the MAPK signaling pathway. When the MAPK signaling pathway is inhibited by its inhibitors, the effects of DHA on SW1353 cells are weakened. Thus, DHA enhances the apoptosis of SW1353 cells through the MAPK signaling pathway.

Long Noncoding RNA-ATB Impairs the Function of Tumor Suppressor miR-126-Mediated Signals in Endometrial Cancer for Tumor Growth and Metastasis.

OBJECTIVE: Long non-coding RNA-ATB (Lnc-ATB) have been reported to promote tumor proliferation and metastasis via regulation of tumor suppressive miRNA-related signals. Patients with endometrial cancer (EC) have advanced stage disease or metastasis have poor prognosis. We here investigated the role of Lnc-ATB in endometrial cancer. METHODS: Endometrial cancer tissues and normal tissues (n = 35) were collected to determine the expression and clinical significance of Lnc-ATB, and bioinformatics analysis was used to predict the miRNA target. siRNA was used to estimate the function of Lnc-ATB in EC cell lines and in vivo. RESULT: The expression of Lnc-ATB is up-regulated in tumor tissues and EC cell lines. Patients with high expressed Lnc-ATB have high FIGO stage and poor tumor differentiation. The tumor suppressor miR-126 interacted with Lnc-ATB. Down-regulated miR-126 negative correlated with FIGO stage and tumor differentiation. Knockdown of Lnc-ATB in RL95 and HEC1A cell lines increased the miR-126 level and impaired the cell vitality, induced caspase-3-related tumor apoptosis and G1/S arrest. However, abrogation of miR-126 by its inhibitors counteracted Lnc-ATB knockdown-induced tumor inhibition via regulation of miR-126 target gene PIK3R2 and Sox2-related apoptosis and cell cycle pathway. Meanwhile, Lnc-ATB knockdown also suppressed the migration and invasion and inhibited TGF-ß-induced epithelial-mesenchymal transition (EMT) phenotype via miR-126. Knockdown of Lnc-ATB in vivo remarkably induced tumor regression via restoration of tumor suppressor miR-126, leading to deceased tumor volume, reduced expression of PCNA and PIK3R2/Sox2 signals and EMT phenotype in tumor tissues. CONCLUSION: These data demonstrate the tumorigenic role of Lnc-ATBs in endometrial cancer via abrogation of tumor suppressor miR-126 signals.

Prognostic implications of decreased microRNA-101-3p expression in patients with non-small cell lung cancer.

To investigate the expression level of microRNA-101-3p (miR-101-3p) and its possible association with progression, prognosis and chemotherapy in patients with non-small cell lung cancer (NSCLC), the Gene Expression Omnibus (GEO) database was used. Quantitative polymerase chain reaction was used to verify the expression in 327 NSCLC and 42 adjacent normal lung tissues, of which 42 viable tissues were paired with nearby normal lung tissues. Based on the Cox regression model, univariate and multivariate analyses were used to address the factors that had effects on overall survival (OS) and disease-free survival (DFS) rate. Data from the GEO database demonstrated that the miR-101-3p expression in NSCLC was downregulated, compared with normal lung cancer. Survival analysis through univariate and multivariate models indicated that the miR-101-3p expression level was a crucial risk factor for OS and DFS in patients with NSCLC. A number of clinical parameters were determined to be associated with miR-101-3p expression, including tumor diameter, lymph node metastasis and tumor-node-metastasis stage. Adjuvant chemotherapy with high expression of miR-101-3p was determined to increase OS and DFS in patients with NSCLC, compared with patients with de novo or low expression of miR-101-3p. The present results demonstrated that miR-101-3p expression levels were associated with NSCLC progression and prognosis, which indicated that miR-101-3p may serve as a biomarker for patients with NSCLC who have received adjuvant chemotherapy.

FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC.

BACKGROUND/AIMS: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. METHODS: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. CONCLUSION: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients.

Tumor suppressive microRNA-124a inhibits stemness and enhances gefitinib sensitivity of non-small cell lung cancer cells by targeting ubiquitin-specific protease 14.

Increasing evidence has shown that microRNAs (miRNAs) play a significant functional role by directly regulating respective targets in cancer stem cell (CSC)-induced non-small cell lung cancer (NSCLC) progression and resistance to therapy. In this study, we found that hsa-miR-124a was downregulated during spheroid formation of the NSCLC cell lines SPC-A1 and NCI-H1650 and NSCLC tissues compared with normal lung cells and tissues. Patients with lower hsa-miR-124a expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, ubiquitin-specific protease 14 (USP14) was confirmed to be a direct target of hsa-miR-124a. Furthermore, concomitant low hsa-miR-124a expression and high USP14 expression were correlated with a shorter median OS and PFS in NSCLC patients. Cellular functional analysis verified that the tumor suppressor hsa-miR-124a negatively regulated cell growth and self-renewal, and promoted apoptosis and gefitinib sensitivity of lung cancer stem cells by suppressing its target gene USP14. Our results provide the first evidence that USP14 is a direct target of hsa-miR-124a, and that hsa-miR-124a inhibits stemness and enhances the gefitinib sensitivity of NSCLC cells by targeting USP14. Thus, hsa-miR-124a and USP14 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC.

Proteogenomic characterization and integrative analysis of glioblastoma multiforme.

Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.

MiR-136 contributes to pre-eclampsia through its effects on apoptosis and angiogenesis of mesenchymal stem cells.

INTRODUCTION: Mesenchymal stem cells (MSCs) play an important role in the pathology of preeclampsia (PE). The survival of MSCs and angiogenesis in the maternal-fetal interface are important for a successful pregnancy. MicroRNA-136 (miR-136) is highly expressed in decidua-derived MSCs (MSCs) from PE compared with healthy donors (NC). The role of the MSCs aberrant expressed miR-136 in PE development is still unclear. In the present study, we examined the impact of miR-136 on the survival of MSCs and angiogenesis in the maternal-fetal interface. METHODS: MSCs were extracted and transfected with miR-136 mimic and interfering RNAs using lipofectamine-2000. Then cell apoptosis were tested using flow cytometry. HUVEC tube formation ability was tested on Matrigel co-cultured with conditioned MSCs supernatants. RESULTS: High level of miR-136 could suppress cell proliferation and promote apoptosis of MSCs through targeting BCL2. It could also impairs HUVEC capillary formation by suppressing VEGF. DISCUSSION: MiR-136 significantly increase the apoptosis and suppress the proliferation of MSCs. It could also inhibit the capillary formation and trophoblast cell invasion. These data suggest that decidua-derived miR-136 that is increased in PE is a potential causal factor of PE.