Role of extracellular LncRNA-SNHG14/miRNA-3940-5p/NAP12 mRNA in colorectal cancer.

BACKGROUND: We aim to identify and analyze the expression of dyregulated RNAs in colorectal cancer (CRC). METHODS: We selected a panel of RNAs specific to CRC composed of Nucleosome Assembly Protein 1 Like 2 (NAP1L2) mRNA, LNCRNA SNHG14 small nucleolar RNA host gene 14 (LNCRNA SNHG14) and homo sapiens microRNA-3940-5p(hsa-miRNA-3940-5p) from genetic and epigenetic databases. Validation of the chosen RNAs was achieved by real time quantitative PCR in sera of patients with CRC, versus controls groups (benign lesions and healthy individual). RESULTS: We found that LLNCRNA SNHG14, hsa-miRNA-3940-5p and NAP1L2 mRNA had an excellent performance characteristics and more superior than CEA, and CA19.9 for differentiating CRC from controls. Combined expression of lncRNA SNHG14- hsa-miR-3940-5p and NAP1L2 mRNA had reached 100% sensitivity with accuracy 93%. Interestingly, serum hsa-miRNA-3940-5p could be an independent prognostic factor in CRC. CONCLUSION: The extracellular lncRNA SNHG14- hsa-miR-3940-5p - NAP1L2 mRNA may aid in CRC management.KEY MESSAGESThe extracellular RNAs provide a potential class of noninvasive biomarkers with high specificity, accuracy and stability for detection of CRC.We used insilico data analysis followed by qPCR for detection of differential NAP1L2 gene expression with the selected epigenetic regulators.Our data presented interesting biomarker panel (NAP1L2 gene, lncRNA-SNHG14 and hsa-miR-3940-5p) that may be potential for CRC diagnosis and prognosis.

circRNAs (hsa_circ_00156, hsa_circ _000224, and hsa_circ _000520) are novel potential biomarkers in hepatocellular carcinoma.

Circular RNAs (circRNAs) are a newly validated type of noncoding RNAs recently found to be deregulated in several human cancers. More accurate and specific noninvasive biomarkers are strongly needed for better diagnosis and prognosis of hepatocellular carcinoma (HCC). We performed a bioinformatics analysis to retrieve a novel panel of circRNAs potentially relevant to HCC. We examined their expression in the sera of 68 patients with HCC, 60 patients with chronic hepatitis C, and 36 healthy controls using quantitative polymerase chain reaction. We examined the performance characteristics of the selected circRNA biomarker panel in comparison with alpha-fetoprotein (AFP). In addition, we performed a survival analysis to correlate between their expression levels and patient survival. The circRNAs hsa_circ _00224 and hsa_circ _00520 showed a strong biomarker potential with relatively high sensitivities and specificities compared with AFP. The combined panel including the three circRNAs showed superior performance characteristics relative to those of AFP. The median follow-up period was 26 months. hsa_circ_00520 expression has been shown to be associated with relapse-free survival (P < 0.005). circRNAs hsa_circ_00156, hsa_circ_000224, and hsa_circ_000520 are novel potential biomarkers of high sensitivity and specificity, which could potentially be used in the diagnosis of HCC.

Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.

AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM. METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A ( ARSA) gene expression with their epigenetic regulators microRNA ( miR-2053) and long noncoding RNA ( lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed. RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM. CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.

Identification of Novel Molecular Network Expression in Acute Myocardial Infarction.

BACKGROUND: In the current study, we aimed to analyze the hypothesis that human myocardial-specific extracellular RNAs expression could be used for acute myocardial injury(AMI) diagnosis. METHODOLOGY: We used bioinformatics' analysis to identify RNAs linked to ubiquitin system and specific to AMI, named, (lncRNA-RP11-175K6.1), (LOC101927740), microRNA-106b-5p (miR-106b-5p) and Anaphase, promoting complex 11 (ANapc11mRNA). We measured the serum expression of the chosen RNAs in 69 individuals with acute coronary syndromes, 31 individuals with angina pectoris without MI and non-cardiac chest pain and 31 healthy control individuals by real-time reverse-transcription PCR. RESULTS: Our study revealed a significant decrease in both lncRNA-RP11-175K6.1 and ANapc11mRNA expression of in the sera samples of AMI patients compared to that of the two control groups alongside with significant upregulation of miR-106b-5p. CONCLUSION: Of note, the investigated serum RNAs decrease the false discovery rate of AMI to 3.2%.

Computational prediction of vaccine potential epitopes and 3-dimensional structure of XAGE-1b for non-small cell lung cancer immunotherapy.

BACKGROUND: XAGE-1b is shown to be overexpressed in lung adenocarcinoma and to be a strong immunogenic antigen among non-small cell lung cancer (NSCLC) patients. However, 3D structure of XAGE-1b is not available and its confirmation has not been solved yet. METHODS: Multiple sequence alignment was run to select the most reliable templates. Homology modeling technique was performed using computer-based tool to generate 3-dimensional structure models, eight models were generated and assessed on basis of local and global quality. Immune Epitope Database (IEDB) tools were then used to determine potential B-Cell epitopes while NetMHCpan algorithms were used to enhance the determination for potential epitopes of both Cytotoxic T-lymphocytes and T-helper cells. RESULTS: Computational prediction was performed for B-Cell epitopes, prediction results generated; 3 linear epitopes where XAGE-1b (13-21) possessed the best score of 0.67, 5 discontinuous epitopes where XAGE-1b (40-52) possessed the best score of 0.67 based on the predicted model of the finest quality. For a potential vaccine design, computational prediction yielded potential Human Leukocyte Antigen (HLA) class I epitopes including HLA-B*08:01-restricted XAGE-1b (3-11) epitope which was the best with 0.2 percentile rank. Regarding HLA Class II epitopes, HLA-DRB1*12:01-restricted XAGE-1b (25-33) was the most antigenic epitope with 5.91 IC50 value. IC50 values were compared with experimental values and population coverage percentages of epitopes were computed. CONCLUSIONS: This study predicted a model of XAGE-1b tertiary structure which could explain its antigenic function and facilitate usage of predicted peptides for experimental validation towards designing immunotherapies against NSCLC.

Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients.

AIM: miRNAs may act as promising diagnostic and prognostic biomarkers of mesothelioma. This study integrates serum  miR-548a-3p and miR-20a expression based on in silico data analysis followed by clinical validation in malignant mesothelioma patients (malignant pleural mesothelioma [MPM]). PATIENTS & METHODS: Serum miR-548a-3p and  miR-20a level was assessed in the serum of patients with MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time PCR. RESULTS: The expression of serum miR-548a-3p and  miR-20a was positive in 91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate between cases and controls. The sensitivity of the combined chosen serum miRNAs reached 100% in the diagnosis of MPM. CONCLUSION: The current work revealed that sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for MPM.

Clinical significance of miRNA-autophagy transcript expression in patients with hepatocellular carcinoma.

AIM: This study integrates autophagy transcripts miRNAs expression based on bioinformatic analysis followed by clinical validation. METHODOLOGY: Cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a level were investigated in the serum and tissue of patients with hepatocellular carcinoma (HCC), chronic hepatitis C and healthy volunteers by quantitative real-time PCR. The prognostic power of this serum RNA panel was explored. RESULTS: The expression of serum cellular jun proto-oncogene mRNA, LAMP2 mRNA, miR-16 and miR-146a were positive in 85.1, 94, 97.1 and 84.2% HCC patients, respectively and they were correlated with tissue levels. Our results suggested that the chosen panel is an independent prognostic factor for survival in patients with HCC. CONCLUSION: The current work provides four RNA-based biomarker panel for HCC diagnosis and prognosis.