Leptospira infection complicated by demyelinating disease: A case report.

Leptospirosis is a zoonotic disease, found worldwide, that is caused by bacteria of the genus Leptospira. People can be infected with Leptospira if they come in direct contact with the urine of an infected animal. Leptospirosis may be associated with demyelinating lesions of the central nervous system. This case report describes a 66-year-old female patient who presented with fever and generalized aches and progressed to unconsciousness within a few hours of admission. Laboratory tests showed Leptospira infection, and brain magnetic resonance imaging revealed acute demyelinating lesions. The patient responded well to penicillin and intravenous methylprednisolone therapy. Leptospirosis presenting with acute disseminated encephalomyelitis is rare. In this patient, an interdisciplinary collaboration involving the neurologist, radiologist, and pathologist was crucial for diagnosis and management. Further studies are warranted to investigate whether there is a correlation between demyelinating lesions and leptospiral infection.

LncRNA SNHG1 promotes renal cell carcinoma progression through regulation of HMGA2 via sponging miR-103a.

BACKGROUND: Long noncoding RNAs (LncRNAs) plays a vital role in tumorigenesis and development. The molecular mechanism of SNHG1 in renal cell carcinoma (RCC) has not been illustrated. The aim of this research was to explore the expression and function of LncRNA SNHG1 in RCC. MATERIAL AND METHODS: The expression of SNHG1 in clinical tissues and RCC cell lines was detected. Luciferase reporter assay was performed to verify the correlation between SNHG1, miR-103a, and HMGA2. CCK-8 assay was performed to examine cell viability. Cell apoptosis was analyzed using flow cytometry. Cell invasion capacity was determined by Transwell assays. The protein level of HMGA2 was analyzed by Western blotting. RESULTS: The expression of SNHG1 markedly increased in RCC tissues and cell lines. Subsequent studies identified SNHG1 as a miRNA sponge for miR-103a. In addition, SNHG1 knockdown and miR-103a overexpression significantly inhibited progression of RCC. miR-103a also regulated HMGA2 levels. CONCLUSION: Our findings showed that SNHG1 was upregulated in RCC cells and tissues. SNHG1 promoted the malignant characteristics of RCC cells. Its regulatory effect may be regulation of HMGA2 by sponging miR-103a. Therefore, Our study facilitates the understanding of SNHG1 function in RCC.

Ingredients, Anti-Liver Cancer Effects and the Possible Mechanism of DWYG Formula Based on Network Prediction.

BACKGROUND: Hepatitis virus infection plays a critical role in liver cancer initiation and development; so the purpose of this study was to investigate the anti-liver cancer effects of DiWuYangGan (DWYG) which was effective for hepatitis. METHODS: Network predictions were performed. Next, several tests, including HPLC, Caco-2 absorption models, MMT, protein chip, Western blotting and H22-tumor-bearing mouse, were carried out to investigate the effects and possible mechanism of DWYG. RESULTS: Network results showed DWYG might be involved in some processes such as STAT cascade. Some target genes may correspondingly participate in these procedures, such as IL-6, CASP3, AKT1, PPAR, and TP53. Diseases associated with DWYG formula may be liver cancer and hepatitis. Potential active compounds might be CUR and ISO. Chemical analysis results showed that ingredients in the formula, including DEO, SCHB, SOLA, SOLB, SCHA, LIQ, ISO, POT, and CHL, could be determined, indicating that DWYG samples for the following experiments were controllable and consistent. Caco-2 absorption of ingredients in DWYG, including DEO, SCHB, SOLA, SOLB, and LIQ, worked very well. In vitro experiment results showed that DWYG could inhibit the growth of cell lines and its effective ingredients might be SCHB, SOLB, SINA, SINB, SOLB, CUR, DEM, BIS, and GER. Further protein results showed that DWYG could upregulate the expressions of some proteins, including ERK1/2, AKT Ser473, BAD Ser112, PRAS40, Thr246, P38, Gsk-3ß, and Ser9. In vivo experiment results showed that DWYG could shrink tumor size, recover ALT and AST, and decrease IL-6 levels. Their possible mechanism might be through the JAK/STAT3 pathway. CONCLUSION: Besides the known pharmacological function of anti-hepatitis, DWYG extract expressed anti-liver cancer effects and the results were consistent partly with network predictions.

Diwu Yanggan Modulates the Wnt/ß-catenin Pathway and Inhibits Liver Carcinogenesis Signaling in 2-AAF/PH Model Rats.

The activation of the Wnt/ß-catenin signaling pathway in oval cells after liver injury is implicated in hepatocarcinogenesis. Diwu Yanggan capsule is a Chinese herbal medicine that has been used for treating liver disorder. The present study aimed to examine the mechanism by which Diwu Yanggan inhibits liver carcinogenesis, and the involvement of the Wnt/ß-catenin signaling pathway. Diwu Yanggan capsule was administered to 2-acetaminofluorene/partial hepatectomy (2-AAF/PH) rats, a murine model of liver injury. The biomarkers of oval cells and key proteins in the Wnt/ß-catenin signaling pathway were assessed on postoperative day 8, 10, 14, 17, 19 and 22. The results showed that treatment with Diwu Yanggan was associated with reduced expression of oval cell and stem cell biomarkers in the 2-AAF/PH animals. The expression pattern of key proteins in the Wnt/ß-catenin pathway was altered in Diwu Yanggan-treated animals, indicating that the Diwu Yanggan treatment accelerated the activation of the Wnt/ß-catenin pathway in the initial stage and contributed to its deactivation in the later stage. Histological findings indicated that hepatocyte proliferation was suppressed in Diwu Yanggan-treated animals, compared with untreated 2-AAF/PH animals. Taken together, Diwu Yanggan capsule may reduce the risk of hepatocarcinogenesis by modulating the Wnt/ß-catenin signaling pathway.

Integrated analysis of a competing endogenous RNA network in renal cell carcinoma using bioinformatics tools.

BACKGROUND: Circular RNAs (circRNAs) are known to be closely involved in tumorigenesis and cancer progression. Nevertheless, their function and underlying mechanisms in renal cell carcinoma (RCC) remain largely unknown. The aim of the present study was to explore their expression, functions, and molecular mechanisms in RCC. METHODS: We downloaded the circRNA expression profiles from Gene Expression Omnibus (GEO) database, and RNA expression profiles from The Cancer Genome Atlas (TCGA) database. A ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Interactions between proteins were analyzed using the STRING database, and hub genes were identified using the cytoHubba app. We also constructed a circRNA-miRNA-hub gene regulatory module. Functional and pathway enrichment analyses were conducted using "DAVID 6.8" and R package "clusterProfiler". RESULTS: About 6 DEcircRNAs, 17 DEmiRNAs, and 134 DEmRNAs were selected for the construction of ceRNA network of RCC. Protein-protein interaction network and module analysis identified 8 hub genes. A circRNA-miRNA-hub gene sub-network was constructed based on 3 DEcircRNAs, 4 DEmiRNAs, and 8 DEmRNAs. GO and KEGG pathway analysis indicated the possible association of DEmRNAs with RCC onset and progression. CONCLUSIONS: These findings together provide a deeper understanding of the pathogenesis of RCC and suggest potential therapeutic targets.

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments.

BACKGROUND/AIMS: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). METHODS: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. RESULTS: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR-30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. Significant pathways including the Mucin type O-glycan biosynthesis pathway, cell cycle pathway and cysteine and methionine metabolism pathway (all P< 0.05) revealed potential roles of the target genes of miR-30d-5p in the oncogenesis of NSCLC. Results from in vitro experiments indicated that miR-30d-5p could attenuate proliferation and viability of NSCLC cells. Among the 12 identified hub genes, nine genes including E2F3, CCNE2, SKP2, CDK6, TFDP1, LDHA, GOT2, DNMT3B and ST6GALNAC1 were validated by Pearson's correlation test and the human protein atlas (HPA) database as targets of miR-30d-5p with higher probability. Specifically, dual luciferase reporter assay confirmed that CCNE2 was directly targeted by miR-30d-5p. CONCLUSION: In summary, miR-30d-5p expression is decreased in NSCLC, and it might play the role as tumor suppressor in NSCLC by regulating target genes.

Clinical significances of p27 in digestive tract cancers: a comprehensive analysis on immunohistochemistry staining, published literatures, microarray and RNA-seq data.

In the present study, we conducted a comprehensive analysis on the clinical roles of p27 protein and p27 gene in digestive tract cancers (DTCs). First, we performed immunohistochemistry staining and found that p27 protein was down-regulated in DTCs. Then we collected 62 publications and calculated the combined hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) to clarify the relationships of p27 protein expression with prognoses and clinicopathological parameters. The overall HRs indicated that the down-regulated p27 protein was an independent prognostic biomarker for overall survival (HR: 1.58, 95% CI: 1.38-1.81, P < 0.0001) but not for disease-free survival and cancer-specific survival. The combined ORs indicated that a low expression of p27 protein was positively related to lymph node metastasis (OR: 2.15, 95% CI: 1.57-2.96, P < 0.0001), distant metastasis (OR: 2.02, 95% CI: 1.12-3.63, P = 0.019) and pathology grading (OR: 2.14, 95% CI: 1.75-2.62, P < 0.0001). Additionally, 60 DTCs-related microarray and RNA-seq datasets were obtained to investigate the expression level and clinical value of p27 gene in DTCs patients. We found that the expression level of p27 gene in DTCs was similar to that in normal controls. And no significant associations of p27 gene expression with prognoses and clinicopathological factors were observed. In conclusion, according to our results, it was p27 protein, but not p27 gene, that can function as an effective biomarker to predict the clinical outcome in patients with DTCs. The down-regulation of p27 protein in DTCs may not result from the altered expression of p27 gene.

miR­539 suppresses proliferation and induces apoptosis in renal cell carcinoma by targeting high mobility group A2.

Renal cell carcinoma (RCC) is one of the most common urinary malignancies with a high rate of morbidity. MicroRNAs (miRNAs) have been shown to be critical post­transcriptional regulators in tumorigenesis. The present study aimed to investigate the effect of miRNA (miR)­539 on the proliferation and apoptosis of RCC. The expression of miR­539 and high mobility group AT­hook 2(HMGA2) were examined in clinical RCC specimens. The 786­O RCC cell line was also used and was transfected with miR­539 mimics or inhibitors. The correlation between miR­539 and HMGA2 was confirmed using a luciferase reporter assay. Cell viability and apoptosis were detected using MTT and flow cytometry assays. The protein levels of HMGA2, AKT, phosphorylated (p)­AKT, mammalian target of rapamycin (mTOR) and p­mTOR were analyzed using western blot analysis. The results revealed that miR­539 was negatively correlated with the expression of HMGA2 in clinical RCC specimens. Further experiments identified HMGA2 as a direct target of miR­539. The overexpression of miR­539 downregulated the expression of HMGA2, reduced cell proliferation and promoted cell apoptosis, whereas the knockdown of miR­539 led to the opposite results. miR­539 also suppressed the phosphorylation of AKT and mTOR, without altering the levels of total AKT and mTOR. Taken together, the results of the present study indicated that miR­539 negatively regulated the expression of HMGA2 in clinical specimens and in vitro. miR539 inhibited cell proliferation and induced apoptosis in RCC cells. This regulatory effect of miR­539 may be associated with the AKT signaling pathway. Therefore, miR­539 may be used as a biomarker for predicting the progression of RCC.

Immunohistochemical distribution of FOXP3+ regulatory T cells in colorectal cancer patients.

Background: Recent studies have focused on less invasive methods for diagnosing and predicting survival outcomes for colorectal cancer (CRC) patients. Objective: We studied the role of the transcription factor forkhead box P3 (FOXP3) in the tumorigenesis of CRC and investigated its prognostic value in survival outcome estimates. Methods: FOXP3+ regulatory T (Treg) cell levels in CRC and adjacent tissues were measured by immunohistochemistry (IHC) and compared statistically. A literature search was conducted on FOXP3+ Treg cell density and survival rates, including overall survival, disease-free survival, and cancer-specific survival. Meta-analyses were then performed to determine the prognostic value of FOXP3+ Treg cell levels in CRC patients. Results: FOXP3+ Treg cells were increased in CRC tissues over adjacent controls according to the IHC results (t = 14.321; P < 0.001) and cell densities in cases with metastases were higher than those without metastasis (P < 0.05). Cases with serosal infiltration showed higher FOXP3+ Treg cell densities compared to cases without infiltration (P < 0.05) and cell densities in cases differentiated to a lower degree than in cases showing a medium to high degree of differentiation (P < 0.05). Moreover, meta-analysis found a high FOXP3+ Treg cells density in CRC tissues (standardized mean differences = 0.30 [95% CI: 0.03-0.57]), which was correlated with better overall patient survival outcome (hazard ratio = 0.749 [95% CI: 0.648-0.867]). Conclusions: Increased FOXP3+ Treg cells may be an effective marker for tumorigenesis and clinical prognostic evaluation for CRC patients.

Utility of miR­133a­3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta­analysis and bioinformatics.

Increasing evidence has demonstrated that microRNA (miR)­133a­3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR­133a­3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR­133a­3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR­133a­3p expression and clinicopathological features of HCC. Eventually, putative targets of miR­133a­3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR­133a­3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=­0.54; 95% confidence interval (CI), ­0.74 to ­0.35; P<0.001]. Consistently, the level of miR­133a­1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR­133a­1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR­133a­3p expression in HCC group was noted (SMD=­0.69; 95% CI, ­1.10 to ­0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR­133a­3p in HCC. The study reveals that miR­133a­3p may function as a tumor suppressor in HCC. The prospective novel pathways and key genes of miR­133a­3p could offer potential biomarkers for HCC; however, the predictions require further confirmation.

The protective value of miR-204-5p for prognosis and its potential gene network in various malignancies: a comprehensive exploration based on RNA-seq high-throughput data and bioinformatics.

PURPOSE: The prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches. MATERIALS AND METHODS: The data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions. Then a meta-analysis was conducted with all TCGA data and relevant studies collected from literature. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. The prospective molecular mechanism of miR-204-5p was also assessed at a functional level with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-to-protein interactions (PPI) network. RESULTS: From TCGA data, the prognostic value of miR-204-5p obviously varied among 20 types of cancers. The pooled HR was 0.928 (95% CI: 0.774-1.113, P = 0.386, 6203 cases of malignancies). For the meta-analysis based on 15 studies from literature, the pooled HR was 0.420 (95% CI: 0.306-0.576, P < 0.001, 1783 cases of malignancies) for overall survival (OS). Furthermore, the combined HR from both TCGA and literature was 0.708 (95% CI: 0.600-0.834, P < 0.001, 7986 cases of malignancies). Subgroup analyses revealed that miR-204-5p could act as a prognostic marker in cancers of respiratory system and digestive system. Functional analysis was conducted on genes predicted as targets (n = 2057) after the overlay genes from six out of twelve software were extracted. Two significant KEGG pathways were enriched (hsa04360: Axon guidance and hsa04722: Neurotrophin signaling pathway). PPI network revealed some hub genes/proteins (CDC42, SOS1, PIK3R1, MAPK1, PLCG1, ESR1, MAPK11, and AR). CONCLUSIONS: The current study demonstrates that over-expression of miR-204-5p could be a protective factor for a certain group of cancers. Clinically, the low miR-204-5p level could gain a predictive value for a poor survival in cancers of respiratory system and digestive system. The detailed molecular mechanisms of miR-204-5p remain to be verified.

High pretreatment plasma D-dimer predicts poor survival of colorectal cancer: insight from a meta-analysis of observational studies.

D-dimer, one of the canonical markers of hypercoagulability, was reported to be a potential prognostic marker of colorectal cancer. However, an inconsistent conclusion existed in several published studies. Thus, we performed this meta-analysis to provide a comprehensive insight into the prognostic role for pretreatment D-dimer in colorectal cancer. Six databases (English: Pubmed, Embase and Web of Science; Chinese: CNKI, Wangfang and VIP) were utilized for the literature retrieval. Hazard ratio (HR) was pooled by Stata 12.0. A total of fifteen studies (2283 cases) corresponded to this meta-analysis and provided available data to evaluate the prognostic role of D-dimer for colorectal cancer. The pooled HR reached 2.167 (95%. CI (confidence interval): 1.672-2.809, P < 0.001) utilizing random effect model due to obvious heterogeneity among the included studies (I2: 73.3%; P < 0.001). To explore the heterogeneity among the studies, we conducted a sensitivity analysis and found a heterogeneous study. After removing it, the heterogeneity reduced substantially (I2: 0%; P = 0.549) and we obtained a more convincing result by fixed effect model (HR = 2.143, 95% CI = 1.922-2.390, P < 0.001, 14 studies with 2179 cases). In summary, high pretreatment plasma D-dimer predicts poor survival of colorectal cancer based on the current evidence. Further prospective researches are necessary to confirm the role of D-dimer in colorectal cancer.

Downregulation of miR­136­5p in hepatocellular carcinoma and its clinicopathological significance.

The clinical significance of microRNA (miR)­136­5p in hepatocellular carcinoma (HCC) has not been verified. Therefore, in the current study, the authors aimed to explore miR­136­5p expression and its clinical significance in HCC, as well as to investigate its potential target genes function. The authors detected the levels of miR­136­5p in 101 pairs of HCC and para­cancer tissues via reverse transcription­quantitative polymerase chain reaction. Gene Expression Omnibus database and the Cancer Genome Atlas (TCGA) database were used to further verify the clinical significance of miR­136­5p expression in HCC. The target genes prediction analysis of miR­136­5p, natural language processing (NLP) analysis of HCC in PubMed and gene functional enrichment analysis were conducted. The miR­136­5p level was markedly downregulated in HCC tissue, compared to para­non­tumor tissue. MiR­136­5p expression decreased in HCC patients with metastasis (P=0.004), advance TNM stage (P<0.001), portal vein tumor embolus (P=0.007) and vaso­invasion (P=0.003), compared with those HCC patients with non­metastasis, early TNM stage, non­portal vein tumor embolus and non­vaso­invasion, respectively. In the TCGA database, downregulated miR­136­5p was also observed in HCC tissue compared to normal liver tissue (P<0.001). There were 178 genes obtained from the overlap between predicted targets and NLP analysis. GO and KEGG pathway analyses revealed some significant pathways related to cancers. Downregulation of miR­136­5p may be responsible for the carcinogenesis and aggressiveness of HCC. miR­136­5p may act as an anti­carcinoma miRNA, which is essential for HCC progression through the regulation of various signaling pathways. Thus, miR­136­5p interaction may provide a novel strategy for HCC treatment.

A comprehensive insight into the clinicopathologic significance of miR-144-3p in hepatocellular carcinoma.

BACKGROUND: Studies which focused on the character of miR-144-3p in hepatocellular carcinoma (HCC) are limited. This study aimed to explore the expression, clinical significance and the potential targets of miR-144-3p in HCC. METHODS: The Cancer Genome Atlas (TCGA) and a cohort of 95 cases of HCC were applied to investigate aberrant miR-144-3p expression in HCC. A meta-analysis was performed to accumulate data on miR-144-3p expression in HCC based on TCGA, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Gene Expression Omnibus (GEO). Additionally, the potential regulatory mechanisms of miR-144-3p in HCC were explored by bioinformatics. RESULTS: MiR-144-3p expression was downregulated distinctly in HCC compared to para-HCC tissue both in TCGA data (8.9139±1.5986 vs 10.7721±0.9156, P<0.001) and in our qRT-PCR validation (1.3208±0.7594 vs 2.6200±0.9263, P<0.001). The meta-analysis based on TCGA, qRT-PCR and GEO data confirmed a consistent result (standard mean difference =-0.854, 95% CI: -1.224 to -0.484, P<0.001). The receiver operating characteristic curve of miR-144-3p gained a significant diagnostic value both in TCGA data (area under the curve [AUC] =0.852, 95% CI: 0.810 to 0.894, P<0.001) and in qRT-PCR validation (AUC =0.867, 95% CI: 0.817 to 0.916, P<0.001), especially in alpha-fetoprotein-negative HCC patients (AUC =0.900, 95% CI: 0.839 to 0.960, P<0.001). Furthermore, we identified 119 potential targets of miR-144-3p in HCC by bioinformatics. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that several significant biologic functions and pathways correlated with the pathogenesis of HCC, including the p53 signaling pathway. CONCLUSION: MiR-144-3p may function as a cancer suppressor microRNA, which is essential for HCC progression through the regulation of various signaling pathways. Thus, interactions with miR-144-3p may provide a novel treatment strategy for HCC in the future.

Clinical Significance and Effect of lncRNA HOXA11-AS in NSCLC: A Study Based on Bioinformatics, In Vitro and in Vivo Verification.

HOXA11 antisense RNA (HOXA11-AS) has been shown to be involved in tumorigenesis and development of different cancers. However, the role of HOXA11-AS in non-small cell lung cancer (NSCLC) remains unclear. In this study, we firstly explored and confirmed the expression of HOXA11-AS in NSCLC tissues and cells. Cytometry, CCK-8, cell scratch, migration, Matrigel invasion and flow cytometry assays were performed to determine the biological impact of HOXA11-AS in vitro. Furthermore, a chick embryo chorioallantoic membrane (CAM) model of NSCLC was constructed to explore the effect of HOXA11-AS on tumorigenicity and angiogenesis in vivo. Additionally, bioinformatics analyses were performed to investigate the prospective pathways of HOXA11-AS co-expressed genes. As results, HOXA11-AS was markedly highly expressed in NSCLC tissues and cells. Furthermore, the proliferation, migration, invasion, tumorigenic and angiogenic ability of NSCLC cells were all inhibited and apoptosis was induced after HOXA11-AS knock-down. HOXA11-AS RNAi also led to cell cycle arrest on G0/G1 or G2/M phase. In addition, the non-small cell lung cancer pathway might be involved in regulating the co-expressed genes of HOXA11-AS in NSCLC. These results indicate that HOXA11-AS plays pivotal roles in NSCLC and it can become a novel therapeutic direction for treating NSCLC.

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer.

Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients. We previously generated a cisplatin-sensitive NPC cell line, S16, from CNE2 cells and found that eIF3a, ASNS and MMP19 are upregulated in S16 cells, which contributes to their cisplatin sensitivity. In this study, we found that BST2 is downregulated in cisplatin-sensitive S16 cells compared with CNE2 cells. Knockdown of BST2 in NPC cells sensitized their response to cisplatin and promoted cisplatin-induced apoptosis, whereas exogenous overexpression of BST2 increased their cisplatin resistance and inhibited cisplatin-induced apoptosis. Further investigation demonstrated that BST2-mediated cisplatin resistance depended on the activation of the NF-κB signaling pathway and consequent upregulation of anti-apoptotic genes, such as Bcl-XL and livin. Moreover, an analysis of clinical data revealed that a high BST2 level might serve as an independent indicator of poor prognosis in patients with locally advanced NPC treated with platinum-based chemoradiotherapy. These findings suggest that BST2 likely mediates platinum resistance in NPC, offering guidance for personalized and precise treatment strategies for patients with NPC.

Microenvironment of liver regeneration in liver cancer.

The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of "tonifying Shen (Kidney) to regulate liver regeneration and repair by affecting stem cells and their microenvironment" can regulate "the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration"; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.

A qRT-PCR and Gene Functional Enrichment Study Focused on Downregulation of miR-141-3p in Hepatocellular Carcinoma and Its Clinicopathological Significance.

BACKGROUND: The clinical significance of miR-141-3p in hepatocellular carcinoma has not been verified. Therefore, we conducted this study to examine miR-141-3p expression and its clinical significance in hepatocellular carcinoma and to investigate the functions of its potential targets. METHODS: The Cancer Genome Atlas database and the Gene Expression Omnibus database were used to explore the aberrant expression of miR-141-3p in hepatocellular carcinoma. Furthermore, we assessed the miR-141-3p levels in 95 hepatocellular carcinoma tissues with 95 matched adjacent tissues using real-time quantitative polymerase chain reaction. Moreover, a target gene prediction analysis of miR-141-3p, a natural language processing analysis for hepatocellular carcinoma using PubMed, and a gene functional enrichment analysis were conducted to search the potential function of miR-141-3p in the pathogenesis of hepatocellular carcinoma. RESULTS: Regarding The Cancer Genome Atlas data, miR-141-3p levels were markedly downregulated in hepatocellular carcinoma tissue compared to para- or nontumor tissue (4.6112 [1.7096] vs 5.3053 [1.4254], P = .045). MiR-141-3p expression was reduced in patients with hepatocellular carcinoma with a low pathologic T stage (P = .006), a low grade (P = .01), elderly hepatocellular carcinoma patients (P = .001), and male patients with hepatocellular carcinoma (P = .01) compared with that in patients with hepatocellular carcinoma with high pathologic T stages, high grades, young patients with hepatocellular carcinoma, and female patients with hepatocellular carcinoma. However, according to the Gene Expression Omnibus database, no significant differences in the expression of miR-141-3p were observed between hepatocellular carcinoma tissue and normal liver tissue (P = .984). Real-time quantitative polymerase chain reaction confirmed a similar trend of decreased miR-141-3p in hepatocellular carcinoma tissue (1.7542 [0.8663] vs 2.5562 [1.7913], P = .001) as observed in The Cancer Genome Atlas. In addition, decreased miR-141-3p levels were detected in the multiple tumor nodes group (P = .004), the metastasis group (P < .001), and the advanced TNM stage group (P = .01), compared to the single tumor nodes group, the nonmetastasis group, and the early TNM stage group. Two hundred eighty-two genes were identified from the overlap between the predicted targets and the natural language processing analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed several significant biological functions and pathways related to the pathogenesis of cancers, including hepatocellular carcinoma. CONCLUSION: Downregulation of miR-141-3p might be responsible for the carcinogenesis and aggressiveness of hepatocellular carcinoma. MiR-141-3p may act as an antitumor microRNA, which is essential for hepatocellular carcinoma progression through the regulation of various signaling pathways. Thus, interactions with miR-141-3p may provide a novel strategy for hepatocellular carcinoma treatment in the future.

Down-regulation of miR-146a-5p and its potential targets in hepatocellular carcinoma validated by a TCGA- and GEO-based study.

Our previous research has demonstrated that miR-146a-5p is down-regulated in hepatocellular carcinoma (HCC) and might play a tumor-suppressive role. In this study, we sought to validate the decreased expression with a larger cohort and to explore potential molecular mechanisms. GEO and TCGA databases were used to gather miR-146a-5p expression data in HCC, which included 762 HCC and 454 noncancerous liver tissues. A meta-analysis of the GEO-based microarrays, TCGA-based RNA-seq data, and additional qRT-PCR data validated the down-regulation of miR-146a-5p in HCC and no publication bias was observed. Integrated genes were generated by overlapping miR-146a-5p-related genes from predicted and formerly reported HCC-related genes using natural language processing. The overlaps were comprehensively analyzed to discover the potential gene signatures, regulatory pathways, and networks of miR-146a-5p in HCC. A total of 251 miR-146a-5p potential target genes were predicted by bioinformatics platforms and 104 genes were considered as both HCC- and miR-146a-5p-related overlaps. RAC1 was the most connected hub gene for miR-146a-5p and four pathways with high enrichment (VEGF signaling pathway, adherens junction, toll-like receptor signaling pathway, and neurotrophin signaling pathway) were denoted for the overlapped genes. The down-regulation of miR-146a-5p in HCC has been validated with the most complete data possible. The potential gene signatures, regulatory pathways, and networks identified for miR-146a-5p in HCC could prove useful for molecular-targeted diagnostics and therapeutics.

Diagnostic and prognostic roles of IRAK1 in hepatocellular carcinoma tissues: an analysis of immunohistochemistry and RNA-sequencing data from the cancer genome atlas.

BACKGROUND: IRAK1 has been repoted to play an essential role in the development of multiple cancers. However, the clinical significance of IRAK1 in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remain unclear. Therefore, we aimed to investigate the role of IRAK1 in the pathogenesis of HCC in this study. MATERIALS AND METHODS: HCC tissues and para-carcinoma tissues were collected for immunohistochemistry (IHC) analysis to evaluate IRAK1 expression. Data of IRAK1 expression were downloaded from the cancer genome atlas (TCGA) for analyzing the clinical significance of IRAK1. Receiver operating characteristic (ROC) curve and survival analyses were carried out to assess the diagnostic and prognostic significance of IRAK1 in IHC and TCGA data. Additionally, we investigated the alteration of IRAK1 gene in HCC from cBioPortal to generate a network of the interaction between IRAK1 and the neighboring genes. The influence of IRAK1 gene alteration on the prognosis of HCC patients was evaluated by survival analysis. RESULTS: Analysis of both IHC and TCGA data revealed a significant upregulation of IRAK1 in HCC tissues. The IHC analysis revealed there was an increasing trend in IRAK1 expression among normal liver tissues, liver cirrhosis tissues, para-carcinoma tissues and HCC tissues. The ROC curves for IHC and TCGA data demonstrated that IRAK1 exhibited a significant diagnostic value for HCC. Moreover, IRAK1 expression was observed to be associated with tumor size, metastasis and T-stage. The survival analysis indicated that the upregulation of IRAK1 predicted a worse overall survival of HCC. Additionally, data from cBioPortal confirmed that 29% of HCC tissues possessed an alteration of the IRAK1 gene. CONCLUSION: IRAK1 may act as an oncogene in the development of HCC with its overexpression in HCC. Moreover, IRAK1 might serve as a promising diagnostic and therapeutic target for HCC.