Time series RNA-seq analysis identifies MAPK10 as a critical gene in diabetes mellitus-induced atrial fibrillation in mice.

Atrial fibrillation (AF) is a major complication of type 2 diabetes mellitus (T2DM) and plays critical roles in the pathogenesis of atrial remodeling. However, the differentially expressed genes in atria during the development of AF induced by hyperglycemia have rarely been reported. Here, we showed time-dependent increased AF incidence and duration, atrial enlargement, inflammation, fibrosis, conduction time and action potential duration in db/db mice, a model of T2DM. RNA sequencing analysis showed that 2256 genes were differentially expressed in the atria at 12, 14 and 16 weeks. Gene Ontology analysis showed that these genes participate primarily in cell adhesion, cellular response to interferon-beta, immune system process, positive regulation of cell migration, ion transport and cellular response to interferon-gamma. Analysis of significant pathways revealed the IL-17 signaling pathway, TNF signaling pathway, MAPK signaling pathway, chemokine signaling pathway, and cAMP receptor signaling. Additionally, these differentially expressed genes were classified into 50 profiles by hierarchical clustering analysis. Twelve of these profiles were significant and comprised 1115 genes. Gene coexpression network analysis identified that mitogen-activated protein kinase 10 (MAPK10) was localized in the core of the gene network and was the most highly expressed gene at different time points. Knockdown of MAPK10 markedly attenuated DM-induced AF incidence, atrial inflammation, fibrosis, electrical disorder and apoptosis in db/db mice. In summary, the present findings revealed that many genes are involved in DM-induced AF and that MAPK10 plays a central role in this disease, indicating that strategies targeting MAPK10 may represent a potential therapeutic approach to treat DM-induced AF.

miR-335-5p suppresses gastric cancer progression by targeting MAPK10.

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

LmjMAPK10 offers protection against Leishmania donovani infection.

AIMS: This study aimed at evaluating the DNA vaccination efficacy of Leishmania major-derived MAPK10 against Leishmania donovani infection. METHODS AND RESULTS: MAPK10 is one of the 15 mitogen-activated protein kinases (MAPKs) of Leishmania major. Herein, we expressed the gene through a mammalian vector and tested whether priming with this gene would offer protection against L donovani infection. We report that LmjMAPK10 DNA vaccination using a mammalian expression vector significantly reduces the parasite burden. The protection is accompanied by host-protective T-cell functions, TH 1-type cytokines and elevated leishmanial antigen-specific IgG2a isotype response. T-cell response to the L donovani/challenge infection is associated with increase in IL-12 and IFN-γ, but reduced IL-10 and IL-4 production. CONCLUSIONS: LmjMAPK10 is cross-protective against L donovani infection.

CircPGM5 regulates Foxo3a phosphorylation via MiR-21-5p/MAPK10 axis to inhibit bladder cancer progression.

Bladder cancer (BC) is one of the most prevalent malignant tumors worldwide, and the incidence is especially higher in males. Extensive evidence has demonstrated the pivotal role of circular RNAs (circRNAs) in BC progression. However, the exact regulatory mechanism of circRNAs in BC remains incompletely elucidated and warrants further exploration. This study screened a novel circRNA-circPGM5 from thousands of circRNAs by high-throughput sequencing. We found that circPGM5, originating from the PGM5 gene, was significantly lower expressed in BC tissues. Quantitative real-time PCR (qRT-PCR) verified that circPGM5 showed relatively low expression in 50 pairs of BC tissues and EJ and T24 cells. Notably, circPGM5 expression was correlated with stage, grade, and lymphatic metastasis of BC. Through RNA-FISH assay, we confirmed that circPGM5 predominantly localized in the cytoplasm. Functionally, overexpression of circPGM5 inhibited the proliferation, migration, and invasion of BC cells in vitro. Remarkably, circPGM5 demonstrated markedly significant tumor growth and metastasis suppression in vivo. Mechanistically, we discovered that circPGM5 upregulated the mitogen-activated protein kinase 10 (MAPK10) expression by influencing the oncogenic miR-21-5p activity through miR-21-5p absorption. This modulation of MAPK10 impacted the phosphorylation of the tumor suppressor Foxo3a in BC. In conclusion, our findings uncovered the tumor-suppressing role of circPGM5 in BC via the miR-21-5p/MAPK10/Foxo3a axis.

Hub genes, key miRNAs and interaction analyses in type 2 diabetes mellitus: an integrative in silico approach.

Diabetes is a rising global metabolic disorder and leads to long-term consequences. As a multifactorial disease, the gene-associated mechanisms are important to know. This study applied a bioinformatics approach to explore the molecular underpinning of type 2 diabetes mellitus through differential gene expression analysis. We used microarray datasets GSE16415 and GSE29226 to identify differentially expressed genes between type 2 diabetes and normal samples using R software. Following that, using the STRING database, the protein-protein interaction network was constructed and further analyzed by Cytoscape software. The EnrichR database was used for Gene Ontology and pathway enrichment analysis to explore key pathways and functional annotations of hub genes. We also used miRTarBase and TargetScan databases to predict miRNAs targeting hub genes. We identified 21 hub genes in type 2 diabetes, some showing more significant changes in the PPI network. Our results revealed that GLUL, SLC32A1, PC, MAPK10, MAPT, and POSTN genes are more important in the PPI network and can be experimentally investigated as therapeutic targets. Hsa-miR-492 and hsa-miR-16-5p are suggested for diagnosis and prognosis by targeting GLUL, SLC32A1, PC, MAPK10, and MAPT genes involved in the insulin signaling pathway. Insight: Type 2 diabetes, as a rising global and multifactorial disorder, is important to know the gene-associated mechanisms. In an integrative bioinformatics analysis, we integrated different finding datasets to put together and find valuable diagnostic and prognostic hub genes and miRNAs. In contrast, genes, RNAs, and enzymes interact systematically in pathways. Using multiple databases and software, we identified differential expression between hub genes of diabetes and normal samples. We explored different protein-protein interaction networks, gene ontology, key pathway analysis, and predicted miRNAs that target hub genes. This study reported 21 significant hub genes and some miRNAs in the insulin signaling pathway for innovative and potential diagnostic and therapeutic purposes.

MiR-223-3p overexpressed adipose mesenchymal stem cell-derived exosomes promote wound healing via targeting MAPK10.

BACKGROUND: Adipose mesenchymal stem cell (AMSC)-derived exosomes are promising novel factors for wound repair and regeneration. This study aimed to explore the potential roles and underlying mechanisms of specific miRNA in wound healing using AMSC-derived exosomes as carriers. METHODS: The expression profiles of GSE197840 were downloaded to screen for differentially expressed miRNAs (DEmiRNAs), and the corresponding genes of the identified miRNAs were predicted. Next, miRNA-mRNA co-expression networks were constructed and the genes in these networks were subjected to functional analysis. miR-223-3p overexpressed AMSCs were then established to isolate exosomes, and the effects of AMSC-derived exosomes carrying miR-223-3p on wound healing and the related potential mechanisms were further investigated in vivo. RESULTS: 35 DEmiRNAs were identified and a co-expression network containing 22 miRNAs and 91 target genes was constructed. Based on the network, miR-223-3p was the hub node and the genes were significantly enriched in 15 GO terms of biological processes and 14 KEGG pathways, including cAMP, PI3K-Akt, cGMP-PKG, neurotrophin signaling pathway, and dopaminergic synapse. Then, miR-223-3p overexpressed AMSCs-derived exosomes were successfully extracted, and miR-223-3p was found to directly bind with MAPK10. In vivo experiments validated that AMSCs-derived exosomal miR-223-3p could promote wound healing, and up-regulated α-SMA, CD31, COL1A1, COL2A1, COL3A1, and down-regulated MAPK10, TNF-α, IL-ß, and IL-6. CONCLUSIONS: AMSC-derived exosomal miR-223-3p may accelerate wound healing by targeting MAPK10.

The Age-Specific Features and Clinical Significance of NRF2 and MAPK10 Expression in HCC Patients.

BACKGROUND: Nuclear factor (erythroid-derived 2)-like 2 (NRF2) functions decline with age; however, cancer cells can hijack its pathways to ensure survival and aggressiveness. Yet, the role of NRF2 in hepatocellular carcinoma (HCC) is rarely investigated in an age-specific manner. This study investigates the expression of NRF2 and its activator (MAPK10) in different age groups of HCC patients, in addition to the age-specific features of NRF2 and MAPK10 interaction and their clinical significance. METHODS: Tumor and near-tumor tissue samples of 181 HCC patients were used to complete a protein expression analysis of NRF2 and MAPK10. Patients' survival and clinical data were collected for clinical analysis. Global databases (TCGA, ICGC) were used to collect MAPK10 genetic mutation and mRNA expression data in patients with HCC, colorectal, stomach, and pancreatic cancers. RESULTS: Our findings revealed an increase in NRF2 protein expression but only in younger HCC patients, along with a decline in MAPK10 ability to activate NRF2 in older patients. We also found an increased MAPK10 genetic mutation rate and decreased mRNA expression in older patients. Low MAPK10 and NRF2 expression levels were associated with shorter survival and poorer prognosis due to positive correlation with microvascular invasion, tumor thrombus, elevated AFP levels, and larger tumor size. CONCLUSION: NRF2 expression and oxidative stress mechanism in HCC patients are influenced by age. This magnifies the need to consider patients' age in treatment strategies and guidelines and re-evaluates the application of studies' age-standardized findings in older patients who are usually excluded from relevant research.

High-throughput RNA sequencing transcriptome analysis of ABC-DLBCL reveals several tumor evasion strategies.

Activated B-cell (ABC) lymphoma, a distinct molecular entity within diffuse large B-cell lymphoma (DLBCL), remains highly incurable, showing a worse response to standard immunochemotherapy. The discouraging results obtained in several clinical trials using proteasome inhibitors, tyrosine kinase inhibitors, or immunomodulators, lead to an intense search for new, potentially druggable biomarkers in DLBCL. In this study, we designed an experimental strategy for DLBCL to discover high- and low-abundance RNA-seq-derived transcripts involved in the oncogenic phenotype in patients diagnosed with ABC-DLBCL. Based on the results of a comparative analysis, 79 DE genes and two enriched gene sets related to metabolism and immunity were selected. Genes related to drug resistance, anti-inflammatory response, and tumor-cell dissemination were found to be up-regulated, while tumor suppressor genes were down-regulated. Then, we searched for the perturbagens most suitable for gene expression profiling (GEP) by iLINCS-CMap. Herein, we present a novel experimental approach that connects the omics signature of DLBCL with potential drugs for more accurate treatments.

Epigenetic identification of mitogen-activated protein kinase 10 as a functional tumor suppressor and clinical significance for hepatocellular carcinoma.

BACKGROUND: Mitogen-activated protein kinase 10 (Mapk10) is a member of the c-jun N-terminal kinases (jnk) subgroup in the MAPK superfamily, and was proposed as a tumor suppressor inactivated epigenetically. Its role in hepatocellular carcinoma (HCC) has not yet been illustrated. We aimed to investigate the expression and epigenetic regulation of mapk10 as well as its clinical significance in HCC. RESULTS: Mapk10 was expressed in almost all the normal tissues including liver, while we found that the protein expression of MAPK10 was significantly downregulated in clinical samples of HCC patients compared with these levels in adjacent normal tissues (29/46, P < 0.0001). Clinical significance of MAPK10 expression was then assessed in a cohort of 59 HCC cases, which indicated its negative expression was significantly correlated with advanced tumor stage (P = 0.001), more microsatellite nodules (P = 0.025), higher serum AFP (P = 0.001) and shorter overall survival time of HCC patients. Methylation was further detected in 58% of the HCC cell lines we tested and in 66% of primary HCC tissues by methylation-specific PCR (MSP), which was proved to be correlated with the silenced or downregulated expression of mapk10. To get the mechanisms more clear, the transcriptional silencing of mapk10 was reversed by pharmacological demethylation, and ectopic expression of mapk10 in silenced HCC cell lines significantly inhibited the colony formation ability, induced apoptosis, or enhanced the chemosensitivity of HCC cells to 5-fluorouracil. CONCLUSION: Mapk10 appears to be a functional tumor suppressor gene frequently methylated in HCC, which could be a valuable biomarker or a new diagnosis and therapy target in a clinical setting.

MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine-cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein-protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

Screening of molecular markers of induced chemotherapy in supraglottic laryngeal squamouscell carcinoma.

OBJECTIVE: To investigate the expressions of MAPK10, c-Jun and Itga6 in laryngeal carcinoma and its influence on the sensitivity to docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy. METHODS: Fifty-seven patients with supraglottic squamous cell carcinoma, who were treated by two cycles of TPF induction chemotherapy in our hospital, were enrolled in this study and divided into groups by chemotherapy resistance or chemotherapy sensitivity. The expressions of mRNA and protein of MAPK10, c-Jun and Itga6 in tumor tissues were evaluated by immunohistochemistry. The consistency of mRNA and protein expressions was tested, and the relation with the clinicopathological features was analyzed. RESULTS: The positive rates of MAPK10 andc-Jun in the tumor tissues of the sensitive group were significantly higher than those of there assistant group, which was 90.48% and 100.00%, respectively. The expression rate of Itga6 was significantly higher in the resistant group, which was 83.33% (P < 0.05). The mRNA levels of MAPK10 and c-Jun were significantly lower in the resistant group than in the sensitive group, whilethemRNA levelof Itga6was significantly higher in the resistant group (P < 0.05). The protein expressions of MAPK10, c-Jun and Itga6 were consistent with their mRNA expressions (P < 0.05). The expressions of MAPK10, c-Jun and Itga6 were not correlatedwithage, gender and tumor diameter (P > 0.05). However, the expressions of MAPK10 and c-Jun were negatively correlated withclinical stage and pathological grading (P < 0.05). Negative correlations between MAPK 10 and Itga6, and between c-Jun and Itga6in tumor tissues were found by Spearman'srank correlation coefficient (P < 0.05). The correlation was also negative in the resistant tumor tissues (P < 0.05). CONCLUSION: The MAPK10 and c-Jun expressions were down-regulated, while the Itga6 expression was up-regulated in the chemo-resistant laryngeal carcinoma, and the expression levels of different factors were correlated witheach other. These factorsmight be important biomarkers for predicting outcomes of TPF chemotherapy in laryngeal carcinoma in the future.

miR-205-3p Functions as a Tumor Suppressor in Ovarian Carcinoma.

Ovarian cancer (OC) represents the most lethal form of gynaecologic cancers in developed countries. To develop a better therapeutic against OC, characterizing new classes of molecular regulators such as microRNAs (miRNAs) involved in OC tumorigenesis becomes immensely important. We used human OC cell lines to study the expression pattern of miRNA-205-3p. We then employed miRNA-205-3p mimic and inhibitor to elucidate its functional role in OC cells. Downstream target of miRNA-205-3p was characterized in OC cells with luciferase gene reporter assay and Western blotting. Its functional role in OC was also investigated with the siRNA approach. Lastly, we assessed the expression change of miRNA-205-3p and its newly identified target in human OC tissues. miR-205-3p was downregulated in five human OC lines tested. Over-expressing miR-205-3p reduced OC cell proliferation and migration. MAPK10 was identified as a direct target of miR-205-3p. Knocking down MAPK10 suppressed OC cell growth and migration. In contrast, knocking down miR-205-3p promoted clonogenicity of primary ovary cells. In clinical samples, miR-205-3p and MAPK10 expressed inversely in accordance with their expression patterns in OC cells. miR-205-3p was shown as a novel tumor suppressor in OC via inhibiting the MAPK10 pathway. This new finding may inspire new personalized treatment for OC.

miR-137-3p Modulates the Progression of Prostate Cancer by Regulating the JNK3/EZH2 Axis.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men worldwide. Early detection of prostate cancer by prostate-specific antigen (PSA) screening still has limitations. The discovery of new candidates is urgent and can provide insights into the mechanism involved in prostate cancer tumorigenesis. METHODS: We conducted a cross-sectional study involving prostate cancer cell lines and clinical samples. qPCR and IHC were used to evaluate the expression of miR-137-3p/JNK3/EZH2. Furthermore, cell growth, migration, invasion, cell cycle and apoptosis were analyzed to describe the function of this axis. Moreover, xenograft models, pathology platforms and TCGA data were generated to confirm the role of the miR-137-3p/JNK3/EZH2 axis. RESULTS: In this study, we determined that miR-137-3p was significantly reduced in prostate cancer, and low expression of miR-137-3p was correlated with tumor stage . The overexpression of miR-137-3p suppressed cell proliferation, migration and invasion in prostate cancer by enhancing cell apoptosis. We also validated JNK3 (MAPK10) as a direct target gene of miR-137-3p. Down-regulation of JNK3 in prostate cancer also inhibited cell proliferation and invasion and promoted apoptosis. Moreover, JNK3 expression was up-regulated and negatively correlated with miR-137-3p in prostate cancer tissues. Furthermore, JNK3 modulated EZH2 expression, which is a key oncogene in prostate cancer. Survival data indicated that patients with high levels of JNK3 and EZH2 had a worse prognosis. CONCLUSION: Collectively, the identification of miR-137-3p and the JNK3/EZH2 pathway might facilitate the development of biomarkers and therapeutic targets for prostate cancer.

19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer.

Zinc-finger proteins (ZFPs) are the largest transcription factor family in mammals, involved in the regulation of multiple physiologic processes including cell differentiation, proliferation, apoptosis and neoplastic transformation. Approximately one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs. Methods: ZNF471 expression and methylation were detected by reverse-transcription PCR and methylation-specific PCR. The impact and mechanism of ectopic ZNF471 expression in esophageal squamous cell carcinoma (ESCC) cells was evaluated in vitro and in vivo. Results: We identified a 19q13 KRAB-ZFP, ZNF471, as a methylated target in ESCC. We further found that ZNF471 is significantly downregulated in ESCC tissues compared with adjacent non-cancer tissues, due to its aberrant promoter CpG methylation, and further confirmed by methylation analysis and treatment with demethylation agent. Restoration of ZNF471 expression in silenced ESCC cells significantly altered cell morphology, induced apoptosis and G0/G1 arrest, and inhibited tumor cell colony formation, viability, migration and invasion. Importantly, ZNF471 was found to activate the expression of MAPK10/JNK3 and PCDH family genes, and further enhance MAPK10 signaling and downstream gene expression through binding to the MAPK10/JNK3 promoter. Conclusion: Our results demonstrate that ZNF471 is an important tumor suppressor and loss of ZNF471 functions hampers MAPK10/JNK3 signaling during esophageal carcinogenesis.

Differentially expressed LncRNAs as potential prognostic biomarkers for glioblastoma.

Glioblastoma (GBM) is the most common and aggressive brain tumor with the poor clinical outcome. LncRNAs (Long non-coding RNAs) play an important role in the occurrence and development of glioblastoma. We aimed to explore the role that lncRNAs play in regulating glioblastoma and the pathways they are enriched in. The expression data of a total of 516 GBM samples were downloaded from TCGA (The Cancer Genome Atlas). We identified the differentially expressed lncRNAs between cancer and normal tissues and performed annotation of differentially expressed lncRNAs to figure out the functions and pathways they were enriched in. Finally, cluster analysis was performed on the expression data of lncRNA and the samples were divided into four kinds, which were then used in the survival analysis. A total of 90 down-regulated lncRNAs and 224 up-regulated lncRNAs were screened out, which were mostly enriched in pathways of Alzhermer's disease and apoptosis. Their neighborhood genes were mostly enriched in genes sets of RTN1 and MAPK10.The characterization of differentially expressed lncRNAs was found out and the mostly enriched pathways were obtained to figure out the regulation mechanism of lncRNA. Our findings may provide evidence of the potential role of lncRNA in the diagnosis, prognosis and target therapy of GBM.

Involvement of miR-29b signaling in the sensitivity to chemotherapy in patients with ovarian carcinoma.

Although the molecular mechanisms driving chemoresistance and relapse of ovarian cancer have been widely studied, the key molecules have not been identified. In this study, the expression of miR-29b messenger RNA (mRNA) and its targeted genes, myeloid cell leukemia sequence 1, mitogen-activated protein kinase 10 (MAPK10), and autophagy-related protein 9A (ATG9A), were investigated in ovarian carcinomas, and their associations with clinicopathological characteristics and survival of patients with ovarian cancer were analyzed. The protein expression of MCL1, MAPK10, and ATG9A was measured using immunohistochemistry. miR-29b mRNA and ATG9A gene mRNA levels were measured by real-time polymerase chain reaction. Results demonstrated that the percentage of MCL1, MAPK10, and ATG9A protein-positive cases were significantly higher, whereas miR-29b was significantly lower in ovarian serous, mucinous, and clear cell carcinomas than that in normal tissues. MAPK10 was significantly associated with higher histopathologic grading. The percentage of positive myeloid cell leukemia sequence 1, ATG9A, and MAPK10 protein expression and low miR-29b mRNA expression were significantly higher in cases with clinical stage III and IV ovarian cancer than in cases with clinical stage II ovarian cancer. High ATG9A protein and low miR-29b mRNA expression were significantly associated with relapse. Univariate Kaplan-Meier analysis showed a negative correlation between MAPK10 or ATG9A protein expression and overall as well as progression-free survival, whereas a positive correlation was observed between miR-29b mRNA expression and overall as well as progression-free survival. Multivariate Cox regression analysis showed that elevated MAPK10 or ATG9A protein and lowered miR-29b mRNA expression in ovarian carcinoma was an independent poor prognostic predictor. Our study suggested that miR-29b mRNA, MAPK10 protein expression, and ATG9A protein expression are closely related to chemosensitivity of ovarian carcinoma.

Ossification of the posterior longitudinal ligament related genes identification using microarray gene expression profiling and bioinformatics analysis.

Ossification of the posterior longitudinal ligament (OPLL) is a kind of disease with physical barriers and neurological disorders. The objective of this study was to explore the differentially expressed genes (DEGs) in OPLL patient ligament cells and identify the target sites for the prevention and treatment of OPLL in clinic. Gene expression data GSE5464 was downloaded from Gene Expression Omnibus; then DEGs were screened by limma package in R language, and changed functions and pathways of OPLL cells compared to normal cells were identified by DAVID (The Database for Annotation, Visualization and Integrated Discovery); finally, an interaction network of DEGs was constructed by string. A total of 1536 DEGs were screened, with 31 down-regulated and 1505 up-regulated genes. Response to wounding function and Toll-like receptor signaling pathway may involve in the development of OPLL. Genes, such as PDGFB, PRDX2 may involve in OPLL through response to wounding function. Toll-like receptor signaling pathway enriched genes such as TLR1, TLR5, and TLR7 may involve in spine cord injury in OPLL. PIK3R1 was the hub gene in the network of DEGs with the highest degree; INSR was one of the most closely related genes of it. OPLL related genes screened by microarray gene expression profiling and bioinformatics analysis may be helpful for elucidating the mechanism of OPLL.