• colorectal cancer
• inflammatory bowel disease
• miRNA
• non-alcoholic fatty liver disease

• Colitis-associated cancer
• Colorectal cancer
• Inflammatory bowel disease
• microRNA

• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/genetics
• Colitis-Associated Neoplasms/diagnosis
• Colitis-Associated Neoplasms/therapy
• Colitis-Associated Neoplasms/genetics
• Gene Expression Regulation, Neoplastic
• Biomarkers, Tumor/genetics
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/diagnosis

• Department of General and Oncological Surgery, Medical University of Lodz

• autoimmune diseases
• bovine milk
• cytokines
• extracellular vesicles
• miRNA

• Animals
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/immunology
• Cattle
• Milk/metabolism
• Milk/immunology
• Humans
• Autoimmune Diseases/metabolism
• Autoimmune Diseases/immunology
• Cytokines/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism

• 013_2023_PTE_RK/3 University of Pecs

• Crohn's disease
• Diagnosis
• Fibrosis
• Inflammation
• Therapy
• miRNA

• Crohn Disease/genetics
• Crohn Disease/therapy
• Crohn Disease/pathology
• MicroRNAs/genetics
• Humans
• Animals
• Inflammation/genetics
• Fibrosis/genetics

• Inflammatory bowel disease (IBD)
• MicroRNA (miRNA)
• Pathogenesis
• Therapy
• miRNA signature

• Humans
• MicroRNAs/genetics
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/therapy
• Animals

• Assiut University

• Colorectal cancer
• Epigenetics
• Inflammatory bowel disease
• Metabolism
• Transition, Biomarkers

• MIR31
• epithelial regeneration
• inflammatory response
• network modeling
• spring-like effect

• National Natural Science Foundation of China

MicroRNAs, as one of the post-transcriptional regulation of genes, play an important role in the development process, cell differentiation and immune defense. The sea cucumber Apostichopus japonicus is an important cold-water species, known for its excellent nutritional and economic value, which usually encounters heat stress that affects its growth and leads to significant economic losses. However, there are few studies about the effect of miRNAs on heat stress in sea cucumbers. In this study, high-throughput sequencing was used to analyze miRNA expression in the body wall of sea cucumber between the control group (CS) and the heat stress group (HS). A total of 403 known miRNAs and 75 novel miRNAs were identified, of which 13 miRNAs were identified as significantly differentially expressed miRNAs (DEMs) in response to heat stress. A total of 16,563 target genes of DEMs were predicted, and 101 inversely correlated target genes that were potentially regulated by miRNAs in response to heat stress of sea cucumbers were obtained. Based on these results, miRNA-mRNA regulatory networks were constructed. The expression results of high-throughput sequencing were validated in nine DEMs and four differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, pathway enrichment of target genes suggested that several important regulatory pathways may play an important role in the heat stress process of sea cucumber, including ubiquitin-mediated proteolysis, notch single pathway and endocytosis. These results will provide basic data for future studies in miRNA regulation and molecular adaptive mechanisms of sea cucumbers under heat stress.

• National Key Research and Development Program of China

• Adenoma/complications
• Adenoma/diagnosis
• Adenoma/genetics
• Biomarkers/metabolism
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/genetics
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Real-Time Polymerase Chain Reaction

Differential microRNA (miRNA or miR) regulation is linked to the development and progress of many diseases, including inflammatory bowel disease (IBD). It is well-established that miRNAs are involved in the differentiation, maturation, and functional control of immune cells. miRNAs modulate inflammatory cascades and affect the extracellular matrix, tight junctions, cellular hemostasis, and microbiota. This review summarizes current knowledge of differentially expressed miRNAs in mucosal tissues and peripheral blood of patients with ulcerative colitis and Crohn’s disease. We combined comprehensive literature curation with computational meta-analysis of publicly available high-throughput datasets to obtain a consensus set of miRNAs consistently differentially expressed in mucosal tissues. We further describe the role of the most relevant differentially expressed miRNAs in IBD, extract their potential targets involved in IBD, and highlight their diagnostic and therapeutic potential for future investigations.

• Colitis, Ulcerative/therapy
• Crohn Disease/diagnosis
• Humans
• Inflammatory Bowel Diseases
• MicroRNAs/genetics

• Danmarks Frie Forskningsfond
• Novo Nordisk Fonden
• Lundbeckfonden
• Poul og Erna Sehested Hansens Fond

• Cancer
• Colorectal cancer
• Crohn's disease
• Diagnosis
• Inflammatory bowel disease
• MicroRNA
• Prognosis
• Targets
• Ulcerative colitis

• Biomarker
• DUX4
• FSHD
• miR-206
• miRNA

• Animals
• Biomarkers/metabolism
• Homeodomain Proteins/genetics
• Homeodomain Proteins/metabolism
• Humans
• Mice
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Muscle, Skeletal/pathology
• Muscular Dystrophy, Facioscapulohumeral/pathology

• R01 AR070432 NIAMS NIH HHS
• National Institute of Arthritis and Musculoskeletal and Skin Diseases

• Autoimmune diseases
• Human Th17 differentiation
• MicroRNAs
• RARB
• miR-141-3p
• miR-200a-3p

• biomarkers
• colitis-associated colorectal cancer
• colorectal cancer
• inflammatory bowel disease
• microRNA

• Carcinogenesis/genetics
• Colitis/complications
• Colitis/genetics
• Colitis/pathology
• Colorectal Neoplasms/complications
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• MicroRNAs/genetics

• in situ hybridization
• inflammatory bowel disease
• miRNA
• pediatric
• quantitative polymerase chain reaction

• Crohn’s disease (CD)
• biomarkers
• circulating miRNA
• colitis-associated cancer (CAC)
• inflammatory bowel disease (IBD)
• microRNA (miRNA)
• ulcerative colitis (UC)

• Crohn's disease
• MicroRNA
• biomarkers
• colon cancer
• metastasis
• ulcerative colitis

Background: The regulatory network of ulcerative colitis (UC)-associated miRNAs is not fully understood. In this study, we aim to investigate the global profile and regulatory network of UC associated miRNAs in the context of dextran sulfate sodium (DSS). Methods: UC was induced in C57BL mice using DSS. Differentially expressed miRNAs were screened by RNA sequencing and subjected to the Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis. RT-qPCR was used to verify the differential expression of miRNAs and candidate target mRNA. Luciferase reporter vector bearing a miRNA binding site was constructed to verify the binding site of the miRNA on mRNA. Results:A total of 95 miRNAs (31 were up-regulated and 64 were down regulated) differentially expressed in the colonic tissues of the UC mice. Among the differentially expressed miRNAs, IL-25 pathway genes were enriched. Subsequent RT-qPCR confirmed a decreased expression of IL-25 and a significant up regulation of IL-25 target miRNAs including mmu-miR-135b-5p, mmu-miR-7239-5p and mmu-miR-691 in UC mice. Conclusion: Using the luciferase assay, we verified the biding sites of mmu-miR-135b-5p and mmu-miR-691 to the IL-25 3ʹUTR. In conclusion, mmu-miR-135b-5p:IL-25 and mmu-miR-691:IL-25 interactions are important pathways that may exert a protective role in UC.

• IL-25
• MicroRNA
• miR-135b-5p
• miR-691
• ulcerative colitis

• Epigenetics
• cancer
• hallmarks

• Inflammatory bowel disease
• colorectal cancer
• epigenetics
• genomics
• inflammatory bowel disease-associated cancer
• molecular pathways

Hypoxia has been particularly associated with poor prognosis in cancer patients. Recent studies have suggested that hypoxia-related miRNAs play a critical role in various cancers, including colorectal cancer (CRC). In the present study, we found 52 differentially expressed miRNAs in HT-29 cells under hypoxic conditions versus normoxic conditions by analyzing the profiles of miRNAs. Using Cox model, we developed a hypoxia-related miRNA signature consisting of four miRNAs, which could successfully discriminate high-risk patients in the Cancer Genome Atlas (TCGA) training cohort (n=381). The prognostic value of this signature was further confirmed in the TCGA testing cohort (n=190) and an independent validation cohort composed of formalin-fixed paraffin-embedded clinical CRC samples (n=220), respectively. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CRC patients. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of this signature was significantly larger than that of any other clinical risk factors or single miRNA alone. A nomogram was constructed for clinical use, which incorporated both the miRNA signature and clinical risk factors and performed well in the calibration plots. Collectively, this novel hypoxia-related miRNA signature was an independent prognostic factor, and it possessed a stronger predictive power in identifying high-risk CRC patients than currently used clinicopathological features.

• colorectal cancer
• hypoxia microRNA signature
• nomogram
• prediction
• prognosis

• colitis
• miR-31
• microRNA
• regulatory T cells
• resveratrol

• colorectal cancer
• disease activity
• disease behaviour
• disease susceptibility
• epigenetic modifications
• inflammatory bowel disease
• therapeutic translation

The inflammatory microenvironment, which mediates the initiation and malignant development of tumors, has been reported to be associated with microRNA (miRNA) dysregulation. In the present study, the expression of miR-139-5p was analyzed in colorectal cancer (CRC) cell lines SW480, HT29, HCT-8, LoVo and HCT116, aiming to investigate the function and mechanism of miR-139-5p in the regulation of the malignant phenotypes of CRC. miR-139-5p expression was found to be considerably downregulated in CRC cell lines compared with the human normal colon mucosal epithelial cell line NCM460. Subsequently, it was demonstrated that overexpression of miR-139-5p in colon cancer cell lines significantly suppressed the cell proliferation in vitro and in vivo. In addition, overexpression of miR-139-5p further inhibited the invasion ability of colon cancer cells in vitro, concomitantly with downregulation of key invasion-associated proteins, including matrix metalloproteinase 9 (MMP9) and MMP7. Furthermore, it was demonstrated that overexpression of miR-139-5p decreased the expression levels of inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), by suppressing nuclear factor (NF)-κB activity. Therefore, these findings collectively indicated that miR-139-5p regulated chronic inflammation by suppressing NF-κB activity in order to inhibit cell proliferation and invasion in CRC, thereby indicating a novel molecular mechanism in CRC therapy.

• chronic inflammation
• colorectal cancer
• invasion
• microRNA-139-5p
• proliferation

• Colitis
• Inflammation
• NF-κB
• STAT3
• Tumorigenesis
• miRNAs

• CAC
• CRC
• IBD
• miR-19a
• miR-21
• miR-31
• miRNAs

• Gene Regulation
• IBD
• Nanoparticle Delivery System
• Posttranscriptional Processing

• Animals
• Biomarkers/metabolism
• Biopsy, Needle
• Case-Control Studies
• China
• Colitis, Ulcerative/pathology
• Crohn Disease/pathology
• Disease Models, Animal
• Humans
• Immunohistochemistry
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/pathology
• Mice
• Mice, Knockout
• MicroRNAs/metabolism
• Microspheres
• RNA, Messenger/metabolism
• Random Allocation
• Regeneration/physiology
• Signal Transduction

• HDAC2
• MCF-7
• cell cycle
• exosome
• halofuginone
• miR-31

• Tongxieyaofang
• Visceral hypersensitivity
• irritable bowel syndrome
• microRNAs

• Animals
• Colon/metabolism
• Colon/pathology
• Down-Regulation
• Gene Expression Regulation
• Hypersensitivity
• Intestinal Absorption
• Intestinal Mucosa
• Irritable Bowel Syndrome/complications
• Irritable Bowel Syndrome/genetics
• Male
• MicroRNAs/genetics
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation

• LY18H030001 Natural Science Foundation of Zhejiang Province
• 2017KY413 Medicine and Health Science and Technology Plan Projects in Zhejiang province
• 2017ZA089 Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province
• 2016ZB071 Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province
• 2015ZZ012 Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province
• 2014ZA030 Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province
• 81573760 National Natural Science Foundation of China
• 2015RCA020 Medical Health Platform Plan Projects of Zhejiang Province
• LY16H030010 Natural Science Foundation of Zhejiang Province

• colorectal cancer
• epigenetics
• genetics
• gut microbiota
• molecule
• ulcerative colitis

Endothelial cell autophagy has a protective role in inhibiting inflammation and preventing the development of atherosclerosis, which may be regulated by microRNA (miR)-155. The present study aimed to investigate the mechanisms of autophagy in the development of atherosclerosis. Human umbilical vein endothelial cells model in vitro and using oxidized low-density lipoprotein (ox-LDL) stimulated cells to simulate the atherosclerosis. MiR-155 mimics, miR-155 inhibitors, and a negative control were respectively transfected in human umbilical vein endothelial cells to analyzed alterations in the expression of miR-155. It was demonstrated that overexpression of miR-155 promoted autophagic activity in oxidized low-density lipoprotein-stimulated human umbilical vein endothelial cells, whereas inhibition of the expression of miR-155 reduced autophagic activity. Overexpression of miR-155 revealed that it regulated autophagy via the phosphatidylinositol-3 kinase (PI3K)/RAC-α serine/threonine-protein kinase (Akt)/mechanistic target of rapamycin pathway (mTOR) signaling pathway. A luciferase reporter assay demonstrated that miR-155 directly bound to the PI3K catalytic subunit a and Ras homolog enriched in brain 3′-untranslated region and inhibited its luciferase activity. Therefore, the results of the present study suggested that miR-155 promoted autophagy in vascular endothelial cells and that this may have occurred via targeting of the PI3K/Akt/mTOR pathway. Thus, miR-155 may be considered as a potential therapeutic target for the treatment of atherosclerosis.

• Ulcerative colitis
• biomarker
• colitis-associated colorectal cancer
• endoscopy
• surveillance

Identification of biological markers predicting the onset of neoplasia in patients with long-standing ulcerative colitis (UC) could allow for risk stratification in this population. In this study, we retrospectively identified subjects with chronic UC who developed colon neoplasia (n = 16) matched to UC patients who never developed neoplasia. RNA was extracted from archived colonic biopsies obtained at an interval of 1–2 years prior and 3–5 years prior to the onset of neoplasia. miRNA expression was assessed using Nanostring arrays in 12 subjects, and significantly up-regulated miRNAs were evaluated by real time pcr in the entire cohort of patients. Expression of miR-215 was also assessed in UC-associated colon cancers and compared to p53 expression. By array analysis, there were 17 significantly down-regulated and 7 significantly up-regulated miRNAs in subjects who later developed neoplasia. miR-215 was significantly up-regulated both 1–2 years prior to the onset of neoplasia (3.5-fold, p < 0.001) and 3–5 years prior to the onset of neoplasia (5.4-fold, p = 0.007). miR-215 expression was also increased in UC-associated colon cancers (5.3-fold, p = 0.03) and adjacent non-dysplastic UC tissue (6.2-fold, p = 0.02). p53 was expressed in 20% of patients prior to the onset of neoplasia and in 67% of UC-associated colon cancers, although was not correlated with miR-215 expression. Our data demonstrates that expression of miR-215 can discriminate patients who progressed to neoplasia from non-progressors as early as 5 years prior to the diagnosis of neoplasia, supporting that this and perhaps other miRNAs could serve as predictive biomarkers to risk stratify patients with chronic UC.

• colon cancer
• miRNA
• neoplasia
• predictive biomarker
• ulcerative colitis

• epithelium
• gut
• inflammation
• interleukin-13
• microRNAs
• ulcerative colitis

• MR/K001035/1 Medical Research Council

• Crohn's disease
• ascending colon mucosa
• mRNAs
• microRNA expression profiles

• cancer
• miR-708
• miR-708-5p
• oncomiR
• tumor suppressor

• R01 AR069044 NIAMS NIH HHS

Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

Cells lining the inner wall of the gut help to absorb nutrients and to protect the body against harmful microbes and substances. Being on the front line of defense means that these cells often sustain injuries. Specialized cells called intestinal stem cells keep the tissues healthy by replacing the damaged and dying cells.

The intestinal stem cells can produce copies of themselves and generate precursors of the gut cells. They also have specific mechanism to protect themselves from cell death. These processes are regulated by different signals that are generated by the cell themselves or the neighboring cells. If these processes get out of control, cells can easily be depleted or develop into cancer cells. Until now, it remained unclear how intestinal stem cells can differentiate between and respond to multiple and simultaneous signals.

It is known that short RNA molecules called microRNA play an important role in the signaling pathways of damaged cells and during cancer development. In the gut, different microRNAs, including microRNA-31,help to keep the gut lining intact. However, previous research has shown that bowel cancer cells also contain high amounts of microRNA-31.

To see whether microRNA-31 plays a role in controlling the signaling systems in intestinal stem cells, Tian, Ma, Lv et al. looked at genetically modified mice that either had too much microRNA-31 or none. Mice with too much microRNA-31 produced more intestinal stem cells and were able to better repair any cell damage. Mice without microRNA-31 gave rise to fewer intestinal stem cellsand had no damage repair, but were able to stop cancer cells in the gut from growing.

The results showed that microRNA-31 in intestinal stem cells helps the cells to divide and to protect themselves from cell death. It controlled and balanced the different types of cell signaling by either repressing or activating various signals. When Tian et al. damaged the stem cells using radiation, the cells increased their microRNA-31 levels as a defense mechanism. This helped the cells to survive and to activate repair mechanisms. Furthermore, Tian et al. discovered that microRNA-31 can enhance the growth of tumors.

These results indicate that microRNA-31 plays an important role both in repairing gut linings and furthering tumor development. A next step will be to see whether cancer cells use microRNA-31 to protect themselves from chemo- and radiation therapy. This could help scientists find new ways to render cancerous cells more susceptible to existing cancer therapies.

• BMP
• Wnt
• colorectal cancer
• developmental biology
• intestinal stem cell
• miR-31
• mouse
• regeneration
• stem cells