• Chronic kidney disease
• NOP14-AS1
• diagnostic value
• miR-326
• potential regulatory mechanisms

• Gastrointestinal stromal tumors
• Methyltransferase-like 3
• N6-methyladenosine
• miR-25-3p

• LncRNA NR2F2-AS1
• Long non-coding RNA
• ceRNA. Nuclear receptor subfamily 2 group F member 2 antisense RNA 1

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tracts and a model for the targeted therapy of solid tumors because of the oncogenic driver mutations in KIT and PDGDRA genes, which could be effectively inhibited by the very first targeted agent, imatinib mesylate. Most of the GIST patients could benefit a lot from the targeted treatment of this receptor tyrosine kinase inhibitor. However, more than 50% of the patients developed resistance within 2 years after imatinib administration, limiting the long-term effect of imatinib. Noncoding RNAs (ncRNAs), the non-protein coding transcripts of human, were demonstrated to play pivotal roles in the resistance of various chemotherapy drugs. In this review, we summarized the mechanisms of how ncRNAs functioning on the drug resistance in GIST. During the drug resistance of GIST, there were five regulating mechanisms where the functions of ncRNAs concentrated: oxidative phosphorylation, autophagy, apoptosis, drug target changes, and some signaling pathways. Also, these effects of ncRNAs in drug resistance were divided into two aspects. How ncRNAs regulate drug resistance in GIST was further summarized according to ncRNA types, different drugs and categories of resistance. Moreover, clinical applications of these ncRNAs in GIST chemotherapies concentrated on the prognostic biomarkers and novel therapeutic targets.

• National Natural Science Foundation of China

• PTEN
• STAT3
• colorectal cancer
• lithocholic acid
• miR21

• Cell Line, Tumor
• Chenodeoxycholic Acid/pharmacology
• Cholic Acid/pharmacology
• Colorectal Neoplasms/pathology
• Deoxycholic Acid/pharmacology
• Detergents/pharmacology
• HCT116 Cells
• HT29 Cells
• Humans
• Lithocholic Acid/pharmacology
• MAP Kinase Signaling System/physiology
• MicroRNAs/genetics
• Mitogen-Activated Protein Kinase 3/metabolism
• PTEN Phosphohydrolase/antagonists & inhibitors
• STAT3 Transcription Factor/metabolism

• 2018R1D1A1B07049918 National Research Foundation of Korea
• 81702413 National Natural Science Foundation of China

• Acute myocardial injury
• Apoptosis
• Cyclosporine a
• Mitochondrial dysfunction
• Obesity
• PI3K/Akt/bad pathway
• Renal ischemia-reperfusion
• Tanshinone IIA

• DNA methylation
• Epigenetics
• HPV
• Warts

Pancreatic cancer is an aggressive disease with a high mortality rate. Radiotherapy is one treatment option within a multimodal therapy approach for patients with locally advanced, non-resectable pancreatic tumors. However, radiotherapy is only effective in about one-third of the patients. Therefore, biomarkers that can predict the response to radiotherapy are of utmost importance. Recently, microRNAs, small non-coding RNAs regulating gene expression, have come into focus as there is growing evidence that microRNAs could serve as diagnostic, predictive and prognostic biomarkers in various cancer entities, including pancreatic cancer. Moreover, their high stability in body fluids such as serum and plasma render them attractive candidates for non-invasive biomarkers. This article describes the role of microRNAs as suitable blood biomarkers and outlines an overview of radiation-induced microRNAs changes and the association with radioresistance in pancreatic cancer.

Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15–20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.

• biomarker
• miRNA
• pancreatic cancer
• personalized medicine
• radioresistance
• radiotherapy
• target

• GIST
• biomarker
• long non-coding RNAs
• microRNA
• therapy

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Gastrointestinal Stromal Tumors/genetics
• Gastrointestinal Stromal Tumors/metabolism
• Gastrointestinal Stromal Tumors/pathology
• Gastrointestinal Stromal Tumors/therapy
• Humans
• Imatinib Mesylate/therapeutic use
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Proto-Oncogene Proteins c-kit/genetics
• Proto-Oncogene Proteins c-kit/metabolism
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• Receptor, Platelet-Derived Growth Factor beta/genetics
• Receptor, Platelet-Derived Growth Factor beta/metabolism

• dasatinib
• gastrointestinal stromal tumor
• next-generation sequencing

The evolution of next-generation sequencing technology has resulted in a generation of large amounts of cancer genomic data. Therefore, increasingly complex techniques are required to appropriately analyze this data in order to determine its clinical relevance. In this study, we applied a neural network-based technique to analyze data from The Cancer Genome Atlas and extract useful microRNA (miRNA) features for predicting the prognosis of patients with lung adenocarcinomas (LUAD). Using the Cascaded Wx platform, we identified and ranked miRNAs that affected LUAD patient survival and selected the two top-ranked miRNAs (miR-374a and miR-374b) for measurement of their expression levels in patient tumor tissues and in lung cancer cells exhibiting an altered epithelial-to-mesenchymal transition (EMT) status. Analysis of miRNA expression from tumor samples revealed that high miR-374a/b expression was associated with poor patient survival rates. In lung cancer cells, the EMT signal induced miR-374a/b expression, which, in turn, promoted EMT and invasiveness. These findings demonstrated that this approach enabled effective identification and validation of prognostic miRNA markers in LUAD, suggesting its potential efficacy for clinical use.

• Cascaded Wx
• lung adenocarcinoma
• machine learning
• microRNA
• prognosis

• Animals
• Cardiotonic Agents/pharmacology
• Cardiotoxicity/metabolism
• Cell Line
• Doxorubicin/toxicity
• Male
• Mice
• Mice, Inbred C57BL
• PTEN Phosphohydrolase/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Rats
• Signal Transduction/drug effects
• Simendan/pharmacology

• AKT
• Cancer
• PI3K
• PTEN
• Targeted therapy

• Apoptosis/physiology
• Cell Line, Tumor
• Cell Proliferation/physiology
• Cell Transformation, Neoplastic/genetics
• Epithelial-Mesenchymal Transition/physiology
• Humans
• Neoplasms/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Phosphatidylinositol 3-Kinases/physiology
• Proto-Oncogene Proteins c-akt/metabolism
• Proto-Oncogene Proteins c-akt/physiology
• Signal Transduction/physiology
• Tumor Microenvironment/physiology

• 81602631 The National Natural Science Foundation of China
• 2016A030310280 Natural Science Foundation of Guangdong Province
• C195015021 Guangzhou Medical University
• 2019A008 The Third Affiliated Hospital of Guangzhou Medical Uiversity

Previous studies have shown that microRNAs (miRNAs) play important roles in the pathogenesis of human cancers. This study aims to clarify the role of miR‐374b in non‐small cell lung cancer (NSCLC).

In this study, RT‐qPCR and western blot analysis were used to measure mRNA and protein expression. The regulatory mechanism of miR‐374b/ITGB1 was investigated by dual‐luciferase reporter, CCK‐8, and transwell assays.

MiR‐374b expression was reduced in NSCLC tissues and associated with lymph node metastasis, tumor stage and prognosis in NSCLC patients. Functionally, overexpression of miR‐374b inhibited cell viability and metastasis in NSCLC. In addition, miR‐374b blocked EMT and promoted p53 expression in NSCLC. MiR‐374b was found to directly target ITGB1. Furthermore, upregulation of ITGB1 weakened the antitumor effect of miR‐374b in NSCLC.

MiR‐374b inhibits the tumorigenesis of NSCLC by downregulating ITGB1 and upregulating p53.

• ITGB1
• miR-374b
• non-small cell lung cancer
• p53

• AKT pathway
• BMI-1
• Gastric cancer
• MiR-498

• Cell Movement/genetics
• Cell Proliferation/genetics
• Humans
• Mitogen-Activated Protein Kinase 7
• Neoplasm Invasiveness/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

High-Grade Serous Ovarian Carcinoma (HGSC) is the most incidental and lethal subtype of epithelial ovarian cancer (EOC) with a high mortality rate of nearly 65%. Recent findings aimed at understanding the pathogenesis of HGSC have attributed its principal source as the Fallopian Tube (FT). To further comprehend the exact mechanism of carcinogenesis, which is still less known, we performed a transcriptome analysis comparing FT and HGSC. Our study aims at exploring new players involved in the development of HGSC from FT, along with their signaling network, and we chose to focus on non-coding RNAs. Non-coding RNAs (ncRNAs) are increasingly observed to be the major regulators of several cellular processes and could have key functions as biological markers, as well as even a therapeutic approach. The most physiologically relevant and significantly dysregulated non-coding RNAs were identified bioinformatically. After analyzing the trend in HGSC and other cancers, MAGI2-AS3 was observed to be an important player in EOC. We assessed its tumor-suppressive role in EOC by means of various assays. Further, we mapped its signaling pathway using its role as a miRNA sponge to predict the miRNAs binding to MAGI2AS3 and showed it experimentally. We conclude that MAGI2-AS3 acts as a tumor suppressor in EOC, specifically in HGSC by sponging miR-15-5p, miR-374a-5p and miR-374b-5p, and altering downstream signaling of certain mRNAs through a ceRNA network.

• Epithelial Ovarian Cancer
• Fallopian Tube
• High Grade Serous Ovarian Cancer
• RNA-sequencing analysis
• competing endogenous RNA
• lncRNA MAGI2-AS3
• microRNA
• non-coding RNA
• tumor suppressor

• PTEN
• dog
• melanoma
• miR-374b
• radiation therapy

• Animals
• Cell Line, Tumor
• Dog Diseases/genetics
• Dog Diseases/radiotherapy
• Dogs
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Melanoma/genetics
• Melanoma/radiotherapy
• Melanoma/veterinary
• MicroRNAs/genetics
• PTEN Phosphohydrolase/genetics
• Radiation Tolerance
• Skin Neoplasms/genetics
• Skin Neoplasms/radiotherapy
• Skin Neoplasms/veterinary
• Melanoma, Cutaneous Malignant

• 17K08107 JSPS KAKENHI

• IL6R
• JAK/STAT signaling pathway
• miR-22
• pancreatic beta-cells
• type 2 diabetes mellitus

Japanese Encephalitis virus (JEV) is a neurotropic ssRNA virus, belonging to the Flaviviridae family. JEV is one of the leading causes of the viral encephalitis in Southeast-Asian countries. JEV primarily infects neurons however, the microglial activation has been reported to further enhance the neuroinflammation and promote neuronal death. The PI3K/AKT pathway has been reported to play an important role in type-I interferon response via IRF3. Phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/AKT pathway, participates in microglial polarization and neuroinflammation. The microRNAs are small non-coding endogenously expressed RNAs, which regulate the gene expression by binding at 3′ UTR of target gene. The human microglial cells were infected with JEV (JaOArS982 strain) and up-regulation of microRNA; hsa-miR-374b-5p was confirmed by qRT-PCR. The genes in PI3K/AKT pathway, over-expression and knock-down studies of hsa-miR-374b-5p with and without JEV infection were analyzed through immuno blotting. The regulatory role of hsa-miR-374b-5p on the expression of type-I interferon was determined by luciferase assays. JEV infection modulated the expression of hsa-miR-374b-5p and PI3K/AKT pathway via PTEN. The over-expression of hsa-miR-374b-5p suppressed the PTEN while up-regulated the AKT and IRF3 proteins, whereas, the knockdown rescued the PTEN expression and suppressed the AKT and IRF3 proteins. The modulation of hsa-miR-374b-5p regulated the type-I interferon response during JEV infection. In present study, we have shown the modulation of PTEN by hsa-miR-374b-5p, which regulated the PI3K/AKT/IRF3 axis in JEV infected microglial cells.

• JEV
• hsa-miR-374b-5p
• human microglial cells
• type-I interferon response
• viral immune evasion

Interleukin-6 (IL-6)-type cytokines share the common receptor glycoprotein 130 (gp130), which activates a signaling cascade involving Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) transcription factors. IL-6 and/or its signaling pathway is often deregulated in diseases, such as chronic liver diseases and cancer. Thus, the identification of compounds inhibiting this pathway is of interest for future targeted therapies. We established novel cellular screening systems based on a STAT-responsive reporter gene (Cypridina luciferase). Of a library containing 538 microRNA (miRNA) mimics, several miRNAs affected hyper-IL-6-induced luciferase activities. When focusing on candidate miRNAs specifically targeting 3′ UTRs of signaling molecules of this pathway, we identified, e.g., miR-3677-5p as a novel miRNA affecting protein expression of both STAT3 and JAK1, whereas miR-16-1-3p, miR-4473, and miR-520f-3p reduced gp130 surface expression. Interestingly, combination treatment with 2 or 3 miRNAs targeting gp130 or different signaling molecules of the pathway did not increase the inhibitory effects on phospho-STAT3 levels and STAT3 target gene expression compared to treatment with single mimics. Taken together, we identified a set of miRNAs of potential therapeutic value for cancer and inflammatory diseases, which directly target the expression of molecules within the IL-6-signaling pathway and can dampen inflammatory signal transduction.

• JAK1
• STAT3
• cancer
• cytokine
• gp130
• inflammation
• interleukin-6
• liver
• microRNAs
• signal transduction

• B cell lymphoma
• biomarkers
• differentiation
• expression
• reactive follicular hyperplasia

• TM3 Leydig cell
• microRNA
• reproductive health
• toxicology
• zearalenone

• AMP-Activated Protein Kinases/genetics
• AMP-Activated Protein Kinases/metabolism
• Animals
• Cell Line
• Cell Survival/drug effects
• Computational Biology
• Environmental Pollutants/toxicity
• Forkhead Box Protein O1/genetics
• Forkhead Box Protein O1/metabolism
• Gene Expression Profiling
• Gene Expression Regulation/drug effects
• Gene Ontology
• High-Throughput Nucleotide Sequencing
• Leydig Cells/cytology
• Leydig Cells/drug effects
• Leydig Cells/metabolism
• Male
• Mice
• MicroRNAs/classification
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Sequence Annotation
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction
• Zearalenone/toxicity
• rap1 GTP-Binding Proteins/genetics
• rap1 GTP-Binding Proteins/metabolism

Gastric cancer (GC) is the third leading cause of cancer-related death. Chemotherapy resistance remains the major reason for GC treatment failure and poor overall survival of patients. Our previous studies have proved that Zuo Jin Wan (ZJW), a traditional Chinese medicine (TCM) formula, could significantly enhance the sensitivity of cisplatin (DDP)-resistant gastric cancer cells to DDP by inducing apoptosis via mitochondrial translocation of cofilin-1. However, the underlying mechanism remains poorly understood. This study aimed to evaluate the effects of ROCK/PTEN/PI3K on ZJW-induced apoptosis in vitro and in vivo. We found that ZJW could significantly activate the ROCK/PTEN pathway, inhibit PI3K/Akt, and promote the apoptosis of SGC-7901/DDP cells. Inhibition of ROCK obviously attenuated ZJW-induced apoptosis as well as cofilin-1 mitochondrial translocation, while inhibition of PI3K had the opposite effects. In vivo, combination treatment of DDP and ZJW (2000 mg/kg) significantly reduced tumor growth compared with DDP alone. Moreover, the combined administration of ZJW and DDP increased the expression of cleaved ROCK and p-PTEN while it decreased p-PI3K and p-cofilin-1, which was consistent with our in vitro results. These findings indicated that ZJW could effectively inhibit DDP resistance in GC by regulating ROCK/PTEN/PI3K signaling and provide a promising treatment strategy for gastric cancer.