Exploring the Key Signaling Pathways and ncRNAs in Colorectal Cancer.

Colorectal cancer (CRC) is the third most prevalent cancer to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, it remains a significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing the urgency for effective diagnostic and therapeutic approaches. CRC development is caused by environmental factors, which mostly lead to the disruption of signaling pathways. Among these pathways, the Wingless/Integrated (Wnt) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, Mitogen-Activated Protein Kinase (MAPK) signaling pathway, Transforming Growth Factor-ß (TGF-ß) signaling pathway, and p53 signaling pathway are considered to be important. These signaling pathways are also regulated by non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They have emerged as crucial regulators of gene expression in CRC by changing their expression levels. The altered expression patterns of these ncRNAs have been implicated in CRC progression and development, suggesting their potential as diagnostic and therapeutic targets. This review provides an overview of the five key signaling pathways and regulation of ncRNAs involved in CRC pathogenesis that are studied to identify promising avenues for diagnosis and treatment strategies.

Exploring the Regulatory Landscape of Dementia: Insights from Non-Coding RNAs.

Dementia, a multifaceted neurological syndrome characterized by cognitive decline, poses significant challenges to daily functioning. The main causes of dementia, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD), have different symptoms and etiologies. Genetic regulators, specifically non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are known to play important roles in dementia pathogenesis. MiRNAs, small non-coding RNAs, regulate gene expression by binding to the 3' untranslated regions of target messenger RNAs (mRNAs), while lncRNAs and circRNAs act as molecular sponges for miRNAs, thereby regulating gene expression. The emerging concept of competing endogenous RNA (ceRNA) interactions, involving lncRNAs and circRNAs as competitors for miRNA binding, has gained attention as potential biomarkers and therapeutic targets in dementia-related disorders. This review explores the regulatory roles of ncRNAs, particularly miRNAs, and the intricate dynamics of ceRNA interactions, providing insights into dementia pathogenesis and potential therapeutic avenues.

Advantages of Laparoscopic Radiofrequency Ablation Over Percutaneous Radiofrequency Ablation in Hepatocellular Carcinoma.

BACKGROUND: Inoperable hepatocellular carcinoma (HCC) can be treated with laparoscopic radiofrequency ablation (LRFA), which is generally a more accurate and accessible procedure than percutaneous RFA (PRFA). However, few studies have compared survival outcomes between LRFA and PRFA in patients with HCC. AIMS: This study aimed to compare the efficacy of LRFA and PRFA for HCC treatment. METHODS: Patients who underwent PRFA or LRFA as an initial treatment modality between April 2005 and April 2016 were enrolled in this study. The overall and recurrence-free survival rates were examined for each patient. Additionally, propensity score matching was performed for both groups. RESULTS: The baseline characteristics of patients in the PRFA and LRFA groups showed several minor differences. Multivariate analysis showed that the RFA method was not a critical determinant of recurrence-free or overall survival (p = 0.069 and p = 0.406). Among patients who underwent RFA as the initial treatment modality, there was no significant effect between either RFA procedures on survival. After propensity score matching, univariate analysis showed a significant difference in overall survival between PRFA and LRFA (p = 0.031). Multivariate analysis showed that LRFA is a strong factor that contributed to an improved overall survival in HCC patients (hazard ratio 0.108, p = 0.040). Furthermore, our data showed that LRFA was able to limit multiple intrahepatic recurrences, as well as prevent marginal recurrence. CONCLUSIONS: LRFA appears to be superior to PRFA in terms of survival. LRFA may help reduce mortality in HCC patients.

The human PTGR1 gene expression is controlled by TE-derived Z-DNA forming sequence cooperating with miR-6867-5p.

Z-DNA, a well-known non-canonical form of DNA involved in gene regulation, is often found in gene promoters. Transposable elements (TEs), which make up 45% of the human genome, can move from one location to another within the genome. TEs play various biological roles in host organisms, and like Z-DNA, can influence transcriptional regulation near promoter regions. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a critical role in the regulation of gene expression. Although TEs can generate Z-DNA and miRNAs can bind to Z-DNA, how these factors affect gene transcription has yet to be elucidated. Here, we identified potential Z-DNA forming sequence (ZFS), including TE-derived ZFS, in the promoter of prostaglandin reductase 1 (PTGR1) by data analysis. The transcriptional activity of these ZFS in PTGR1 was confirmed using dual-luciferase reporter assays. In addition, we discovered a novel ZFS-binding miRNA (miR-6867-5p) that suppressed PTGR1 expression by targeting to ZFS. In conclusion, these findings suggest that ZFS, including TE-derived ZFS, can regulate PTGR1 gene expression and that miR-6867-5p can suppress PTGR1 by interacting with ZFS.

Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases.

BACKGROUND: Transposable elements (TEs) are known to be inserted into genome to create transcript isoforms or to generate long non-coding RNA (lncRNA) sequences. The insertion of TEs generates a gene protein sequence within the genome, but also provides a microRNA (miRNA) regulatory region. OBJECTIVE: To determine the effect of gene sequence changes caused by TE insertion on miRNA binding and to investigate the formation of an overlapping lncRNA that represses it. METHODS: The distribution of overlapping regions between exons and TE regions with lncRNA was examined using the Bedtools. miRNAs that can bind to those overlapping regions were identified through the miRDB web program. For TE-lncRNA overlapping genes, bioinformatic analysis was conducted using DAVID web database. Differential expression analysis was conducted using data from the GEO dataset and TCGA. RESULTS: Most TEs were distributed more frequently in untranslated regions than open reading frames. There were 30 annotated TE-lncRNA overlapping genes with same strand that could bind to the same miRNA. As a result of identifying the association between these 30 genes and diseases, TGFB2, FCGR2A, DCTN5, and IFI6 were associated with breast cancer, and HMGCS1, FRMD4A, EDNRB, and SNCA were associated with Alzheimer's disease. Analysis of the GEO and TCGA data showed that the relevant expression of miR-891a and miR-28, which bind to the TE overlapping region of DCTN5 and HMGCS1, decreased. CONCLUSION: This study indicates that the interaction between TE-lncRNA overlapping genes and miRNAs can affect disease progression.

Identification of microRNAs Derived from Transposable Elements in the Macaca mulatta (Rhesus Monkey) Genome.

Transposable elements (TEs) are mobile DNA entities that can move within the host genome. Over long periods of evolutionary time, TEs are typically silenced via the accumulation of mutations in the genome, ultimately resulting in their immobilization. However, they still play an important role in the host genome by acting as regulatory elements. They influence host transcription in various ways, one of which as the origin of the generation of microRNAs (miRNAs), which are so-called miRNAs derived from TEs (MDTEs). miRNAs are small non-coding RNAs that are involved in many biological processes by regulating gene expression at the post-transcriptional level. Here, we identified MDTEs in the Macaca mulatta (rhesus monkey) genome, which is phylogenetically close species to humans, based on the genome coordinates of miRNAs and TEs. The expression of 5 out of 17 MDTEs that were exclusively registered in M. mulatta from the miRBase database (v22) was examined via quantitative polymerase chain reaction (qPCR). Moreover, Gene Ontology analysis was performed to examine the functional implications of the putative target genes of the five MDTEs.

Human Endogenous Retrovirus-H-Derived miR-4454 Inhibits the Expression of DNAJB4 and SASH1 in Non-Muscle-Invasive Bladder Cancer.

Although most human endogenous retroviruses (HERVs) have been silenced and lost their ability to translocate because of accumulated mutations during evolution, they still play important roles in human biology. Several studies have demonstrated that HERVs play pathological roles in numerous human diseases, especially cancer. A few studies have revealed that long non-coding RNAs that are transcribed from HERV sequences affect cancer progression. However, there is no study on microRNAs derived from HERVs related to cancer. In this study, we identified 29 microRNAs (miRNAs) derived from HERV sequences in the human genome. In particular, we discovered that miR-4454, which is HERV-H-derived miRNA, was upregulated in non-muscle-invasive bladder cancer (NMIBC) cells. To figure out the effects of upregulated miR-4454 in NMIBC, genes whose expression was downregulated in NMIBC, as well as tumor suppressor genes, were selected as putative target genes of miR-4454. The dual-luciferase assay was used to determine the negative relationship between miR-4454 and its target genes, DNAJB4 and SASH1, and they were confirmed to be promising target genes of miR-4454. Taken together, this study suggests that the upregulation of miR-4454 derived from HERV-H in NMIBC reduces the expression of the tumor suppressor genes, DNAJB4 and SASH1, to promote NMIBC progression.

Serum procalcitonin levels can be used to differentiate between inflammatory and non-inflammatory diarrhea in acute infectious diarrhea.

In this study, we assess the possibility of using procalcitonin levels to differentiate between inflammatory diarrhea and non-inflammatory diarrhea in acute infectious diarrhea.We reviewed the records of 1176 patients who had symptoms of diarrhea, fever (≥37.8 °C), and abdominal pain between March 2011 and May 2015. After applying exclusion criteria, a sample of 514 patients was considered for study. The patient sample was divided into Group A and Group B for inflammatory diarrhea and non-inflammatory diarrhea, respectively. The assessment involved comparing the laboratory characteristics with the clinical characteristics of the groups.The characteristics of Group A, such as white blood cell (WBC), C-reactive protein (CRP), absolute neutrophil count (ANC), and procalcitonin levels, were relatively higher than those of Group B (P < .001 for Group A). A receiver operator characteristic (ROC) analysis revealed that the highest area-under-the-curve (AUC) value of procalcitonin (0.797; 95% confidence interval [CI] [0.760, 0.831]; P < .001), could be used to differentiate between the 2 groups. Procalcitonin exhibited a sensitivity and a specificity of 87.03% and 68.75%, respectively, at a 0.08 ng/mL cut-off level.Procalcitonin was a good candidate biomarker of inflammatory diarrhea than other inflammatory markers.

Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma: Is it a significant prognostic factor?

The purpose of this study was to evaluate the prognostic impact of endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma.This retrospective study was based on medical records from a single tertiary medical center. The records of 317 patients with esophageal squamous cell carcinoma treated with surgery or definitive chemoradiotherapy (CRT) between January 2009 and March 2016 were reviewed. Finally, we retrieved the data on 168 consecutive patients. These 168 patients were divided into 2 groups based on their endoscopic traversability findings: Group A (the endoscope traversable group), and Group B (the endoscope non-traversable group). We then retrospectively compared the clinical characteristics of these 2 groups.The endoscope non-traversable group (Group B) revealed an advanced clinical stage, a poor Eastern Cooperative Oncology Group (ECOG) score, a lower serum albumin level, a higher rate of requirement for esophageal stent insertion and definitive CRT as initial treatment than the endoscope traversable group (Group A). Patients with endoscope traversable cancer showed a significantly higher 3-year overall survival and 3-year relapse-free survival than patients who were endoscope non-traversable (53.8% vs 17.3%, P < .001 and 71.1% vs 45.3%, P = .003, respectively). Upon multivariate analysis of patients with locally advanced esophageal squamous cell carcinoma treated with definitive CRT, the serum albumin level <3.5 g/dL and endoscopic non-traversability were significant negative factors of survival.Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma treated with definitive CRT is a significant prognostic factor.

Risk Factors for Dieulafoy Lesions in the Upper Gastrointestinal Tract.

BACKGROUND/AIMS: The purpose of this study is to verify the risk factors associated with Dieulafoy lesion formation in the upper gastrointestinal tract. METHODS: A case-control study was performed by reviewing the electronic medical records of 42 patients who were admitted to a tertiary medical center in the Daejeon region for Dieulafoy lesions from September 2008 to October 2013, and the records of 132 patients who were admitted during the same period and who underwent endoscopic examination for reasons other than bleeding. We analyzed clinical and endoscopic findings retrospectively, and searched for risk factors associated with Dieulafoy lesion formation. RESULTS: All 42 patients diagnosed with Dieulafoy lesion had accompanying bleeding, and the location of the bleeding was proximal in 25 patients (59.5%), the middle portion in seven patients (16.7%), and distal in 10 patients (23.8%). Antiplatelet agents (p=0.022) and alcohol (p=0.001) use showed statistically significant differences between the two groups. The odds ratios (95% confidence intervals) of the two factors were 2.802 (1.263 to 6.217) and 3.938 (1.629 to 9.521), respectively. CONCLUSIONS: This study showed that antiplatelet agents and alcohol consumption were risk factors associated with Dieulafoy lesion formation in the upper gastrointestinal tract.