Identification of a prognosis-related ceRNA network in cholangiocarcinoma and potentially therapeutic molecules using a bioinformatic approach and molecular docking.

Cholangiocarcinoma (CCA) is a highly malignant disease with a poor prognosis, and mechanisms of initiation and development are not well characterized. It is long noncoding RNAs (lncRNAs) acting as miRNA decoys to regulate cancer-related RNAs in competing endogenous RNA (ceRNA) networks that suggest a possible molecular mechanism in CCA. The current study aims to find potential prognosis biomarkers and small molecule therapeutic targets based on the construction of a CCA prognosis-related ceRNA network. A transcriptome dataset for CCA was downloaded from the TCGA database. Differentially expressed lncRNAs (DElncRNAs), DEmiRNAs and DEmRNAs were identified based on the differential expression and a DEceRNA network was constructed using predicted miRNA-lncRNA and miRNA-mRNA interactions. Heat maps, PCA analysis, and Pathway enrichment analysis and GO enrichment analysis were conducted. The prognostic risk model and molecular docking were constructed based on identified key ceRNA networks. A DElncRNA-miRNA-mRNAs network consisting of 434 lncRNA-miRNA pairs and 284 miRNA-mRNA pairs with 200 lncRNAs, 21 miRNAs, and 245 mRNAs was constructed. There were three lncRNAs (AC090772.1, LINC00519, and THAP7-AS1) and their downstream mRNAs (MECOM, MBNL3, RCN2) screened out as prognostic factors in CAA. Three key networks (LINC00519/ hsa-mir-22/ MECOM, THAP7-AS1/hsa-mir-155/MBNL3, and THAP7-AS1/hsa-mir-155/RCN2) were identified based on binding sites prediction and survival analysis. A prognostic risk model was established with a good predictive ability (AUC = 0.66-0.83). Four anticancer small molecules, MECOM and 17-alpha-estradiol (-7.1 kcal/mol), RCN2 and emodin (-8.3 kcal/mol), RCN2 and alpha-tocopherol (-5.6 kcal/mol), and MBNL3 and 17-beta-estradiol (-7.1 kcal/mol) were identified. Based on the DEceRNA network and Kaplan-Meier survival analysis, we identified three important ceRNA networks associated with the poor prognosis of CCA. Four anti-cancer small molecules were screened out by computer-assisted drug screening as potential small molecules for the treatment of CCA. This study provides theoretical support for the development of ceRNA network-based drugs to improve the prognosis of CCA.

Contribution of upregulated aminoacyl-tRNA biosynthesis to metabolic dysregulation in gastric cancer.

BACKGROUND AND AIM: Metabolic reprogramming is characterized by dysregulated levels of metabolites and metabolic enzymes. Integrated metabolomic and transcriptomic data analysis can help to elucidate changes in the levels of metabolites and metabolic enzymes, screen the core metabolic pathways, and develop novel therapeutic strategies for cancer. METHODS: Here, the metabolome of gastric cancer tissues was determined using liquid chromatography-mass spectrometry. The transcriptome data from The Cancer Genome Atlas dataset were integrated with the liquid chromatography-mass spectrometry data to identify the common dysregulated gastric cancer-specific metabolic pathways. Additionally, the protein expression and clinical significance of key metabolic enzymes were examined using a gastric cancer tissue array. RESULTS: Metabolomic analysis of 16 gastric cancer tissues revealed that among the 15 dysregulated metabolomic pathways, the aminoacyl-tRNA biosynthesis pathway in the gastric tissues was markedly upregulated relative to that in the adjacent noncancerous tissues, which was consistent with the results of transcriptome analysis. Bioinformatic analysis revealed that among the key regulators in the aminoacyl-tRNA biosynthesis pathway, the expression levels of threonyl-tRNA synthetase (TARS) and phenylalanyl-tRNA synthetase (FARSB) were correlated with tumor grade and poor survival, respectively. Additionally, gastric tissue array data analysis indicated that TARS and FARSB were upregulated in gastric cancer tissues and were correlated with poor prognosis and tumor metastasis. CONCLUSIONS: This study demonstrated that the aminoacyl-tRNA biosynthesis pathway is upregulated in gastric cancer and both TARS and FARSB play key roles in the progression of gastric cancer. Additionally, a novel therapeutic strategy for gastric cancer was proposed that involves targeting the aminoacyl-tRNA biosynthesis pathway.

The role of non-coding RNA on macrophage modification in tuberculosis infection.

Tuberculosis (TB), a serious disease caused by Mycobacterium tuberculosis (Mtb), remains the world's top infectious killer. It is well-established that TB can circumvent the host's immune response for long-term survival. Macrophages serve as the major host cells for TB growth and persistence and their altered functions are critical for the response of the host defense against TB exposure (elimination, latency, reactivation, and bacillary dissemination). Noncoding RNAs are crucial posttranscriptional regulators of macrophage discrimination. Therefore, this review highlights the regulatory mechanism underlying the relationship between noncoding RNAs and macrophages in TB infection, which may facilitate the identification of potential therapeutic targets and effective diagnosis biomarkers for TB disease.

The prognostic significance of preoperative serum albumin in urothelial carcinoma: a systematic review and meta-analysis.

Preoperative serum albumin has been considered to be closely correlated with the prognosis of various cancers, including urothelial carcinoma (UC). However, to date, this conclusion remains controversial. The aim of this meta-analysis is to investigate the prognostic significance of preoperative serum albumin in UC. A literature search was performed in PubMed, Web of Science, Embase, and Cochrane Library up to 4 July 2017. Herein, a total of 15506 patients from 23 studies were enrolled in our meta-analysis. Decreased preoperative serum albumin level predicted poor overall survival (OS) (HR = 1.88, 95% CI: 1.44-2.45, P<0.0001), cancer-specific survival (CSS) (HR = 2.03, 95% CI: 1.42-2.90, P=0.0001), recurrence-free survival (HR = 1.85, 95% CI: 1.15-2.97, P=0.01), 30-day complications (30dCs) after surgery (odds ratio (OR) = 1.93, 95% CI: 1.16-3.20, P=0.01), and 90-day mortality after surgery (OR = 4.24, 95% CI: 2.20-8.16, P<0.001). The subgroup analyses indicated that low preoperative serum albumin level is still positively associated with a worse prognosis of UC based on ethnicity, cut-off value, tumor type, analyses type, and sample size. Our meta-analysis indicated that reduced preoperative serum albumin level was a predictor of poor prognosis of UC.