Hypoxia-inducible microRNA-155 negatively regulates epithelial barrier in eosinophilic esophagitis by suppressing tight junction claudin-7.

MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. MiR-155 localization using in situ hybridization (ISH) in patient biopsies and intra-epithelial compartmentalization of miR-155 show expression predominantly within the basal epithelia. Epithelial miR-155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR-155 stable overexpression induced a functionally deficient epithelial barrier in 3D air-liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR-155 showed notable dilated intra-epithelial spaces. Unbiased RNA-sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin-7. Together, our data reveal a previously unappreciated role for miR-155 in mediating epithelial barrier dysfunction in esophageal inflammation.

B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren's Disease: A Pilot Monocentric Exploratory Study.

Primary Sjögren's disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin's lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren's disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren's disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren's disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren's disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren's disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren's disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren's disease, profoundly impacting the risk of NHL development.

[Correlations Between the Expression of MicroRNA-155 and Suppressor of Cytokine Signaling 1 in Colonic Mucosal Tissue and Disease Severity in Patients With Ulcerative Colitis].

Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal tissue of patients with ulcerative colitis (UC) and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group (n=85) and a remission stage group (n=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were assigned into a mild group (n=35),a moderate group (n=30),and a severe group (n=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy results after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quantitative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The correlations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regulated level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue (all P<0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe (all P<0.001).The modified Mayo score was positively correlated with the miR-155 level and negative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients (all P<0.001).The high miR-155 level (OR=2.762,95%CI=1.284-5.944,P=0.009),low mRNA level of SOCS1 (OR=2.617,95%CI=1.302-5.258,P=0.007),and modified Mayo score≥12 points (OR=3.232,95%CI=1.450-7.204,P=0.004) were all risk factors for severe disease in the UC patients at the active stage.The area under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the active stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.

Roles of the miR-155 in Neuroinflammation and Neurological Disorders: A Potent Biological and Therapeutic Target.

Neuroinflammation plays a crucial role in the development and progression of neurological disorders. MicroRNA-155 (miR-155), a miR is known to play in inflammatory responses, is associated with susceptibility to inflammatory neurological disorders and neurodegeneration, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis as well as epilepsy, stroke, and brain malignancies. MiR-155 damages the central nervous system (CNS) by enhancing the expression of pro-inflammatory cytokines, like IL-1ß, IL-6, TNF-α, and IRF3. It also disturbs the blood-brain barrier by decreasing junctional complex molecules such as claudin-1, annexin-2, syntenin-1, and dedicator of cytokinesis 1 (DOCK-1), a hallmark of many neurological disorders. This review discusses the molecular pathways which involve miR-155 as a critical component in the progression of neurological disorders, representing miR-155 as a viable therapeutic target.

Live to die another day: novel insights may explain the pathophysiology behind smoker's paradox in SARS-CoV-2 infection.

The severe acute respiratory coronavirus 2 (SARS-CoV-2) infection demonstrates a highly variable and unpredictable course. Several reports have claimed a smoker's paradox in coronavirus disease 2019 (COVID-19), in line with previous suggestions that smoking is associated with better survival after acute myocardial infarction and appears protective in preeclampsia. Several plausible physiological explanations exist accounting for the paradoxical observation of smoking engendering protection against SARS-CoV-2 infection. In this review, we delineate novel mechanisms whereby smoking habits and smokers' genetic polymorphism status affecting various nitric oxide (NO) pathways (endothelial NO synthase, cytochrome P450 (CYP450), erythropoietin receptor (EPOR); ß-common receptor (ßcR)), along with tobacco smoke modulation of microRNA-155 and aryl-hydrocarbon receptor (AHR) effects, may be important determinators of SARS-CoV-2 infection and COVID-19 course. While transient NO bioavailability increase and beneficial immunoregulatory modulations through the above-mentioned pathways using exogenous, endogenous, genetic and/or therapeutic modalities may have direct and specific, viricidal SARS-CoV-2 effects, employing tobacco smoke inhalation to achieve protection equals self-harm. Tobacco smoking remains the leading cause of death, illness, and impoverishment.

Adenovirus-IL-10 relieves chronic rejection after mouse heart transplantation by inhibiting miR-155 and activating SOCS5.

Objective: Chronic rejection remains the main factor that influence long-term survival of patients after heart transplantation. Interleukin-10 (IL-10) play critical role in macrophages-mediated transplant immune responses. We investigated the mechanism of IL-10 in macrophage related chronic rejection after mouse heart transplantation. Methods: Mouse heart transplant chronic rejection model was established to evaluate pathological changes in the allograft. Myocardial interstitial fibrosis, apoptosis, and inflammatory factor levels were detected in ad-IL-10-treated mice. The positive iNOS+ and Arg-1+ expressions, macrophage subset changes, and the proportion of regulatory T-cells (Tregs) and TIGIT+ Tregs were quantified by flow. In in vitro experiments, ad-IL-10 was transfected into macrophages followed by detection of apoptosis, phagocytosis, and CD163, CD16/32, and CD206 expression. The expression and relationships between IL-10, miR-155, and SOCS5 were also detected and verified. A rescue experiment was performed to evaluate macrophage function through the combined treatment of ad-IL-10 and overexpression of miR-155. Results: Significantly decreased IL-10 expression in chronic rejection during mouse heart transplantation was observed. Ad-IL-10-treated mice showed decreased pathological injury, perivascular fibrosis, apoptosis, inflammation, and iNOS+ and CD16/32+ expression, and increased Treg/TIGIT+ Treg cell, Arg-1+ and CD206+ cell proportion. Ad-IL-10-treated macrophages in vitro showed reduced apoptosis, improved phagocytosis, and M2 polarization. Mechanically, IL-10 negatively regulated miR-155 to activate SOCS5. Overexpression of miR-155 reversed IL-10 mediated-positive regulation of macrophage function. Conclusion: IL-10 downregulated miR-155 and activated SOCS5, thereby promoting macrophage M2 polarization to relieve chronic rejection after heart transplantation.

A highly sensitive colorimetric DNA sensor for MicroRNA-155 detection: leveraging the peroxidase-like activity of copper nanoparticles in a double amplification strategy.

A novel and highly sensitive colorimetric DNA sensor for determination of miRNA-155 at attomolar levelsis presented that combines the peroxidase-like activity of copper nanoparticles (CuNPs) with the hybridization chain reaction (HCR) . The utilization of CuNPs offers advantages such as strong interaction with double-stranded DNA, excellent molecular recognition, and mimic catalytic activity. Herein, a capture probe DNA (P1) was immobilized on carboxylated magnetic beads (MBs), allowing for amplified immobilization due to the 3D surface. Subsequently, the presence of the target microRNA-155 led to the formation of a sandwich structure (P2/microRNA-155/P1/MBs) when P2 was introduced to the modified P1/MBs. The HCR reaction was then triggered by adding H1 and H2 to create a super sandwich (H1/H2)n. Following this, Cu2+ ions were attracted to the negatively charged phosphate groups of the (H1/H2)n and reduced by ascorbic acid, resulting in the formation of CuNPs, which were embedded into the grooves of the (H1/H2)n. The peroxidase-like activity of CuNPs catalyzed the oxidation reaction of 3,3',5,5'-Tetramethylbenzidine (TMB), resulting in a distinct blue color measured at 630 nm. Under optimal conditions, the colorimetric biosensor exhibited a linear response to microRNA-155 concentrations ranging from 80 to 500 aM, with a detection limit of 22 aM, and discriminate against other microRNAs. It was also successfully applied to the determination of microRNA-155 levels in spiked human serum.

MicroRNA-155 targets SOCS1 to inhibit osteoclast differentiation during orthodontic tooth movement.

BACKGROUND: MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms. METHODS: In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155. RESULTS: During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155. CONCLUSIONS: Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.

MicroRNA-155 (miR-155) as an accurate biomarker of periodontal status and coronary heart disease severity: a case-control study.

BACKGROUND: Increasing evidence supports associations between periodontal disease and coronary heart disease (CHD). This case-control study evaluated whether inflammatory regulator, microRNA-155 (miR-155), could be utilised as a biomarker of periodontitis and/or CHD. METHODS: Of 120 participants, 30 patients had clinically healthy periodontium (controls, C), 30 patients had generalized periodontitis (P), 30 patients had CHD and clinically healthy periodontium (AS-C); and 30 patients had CHD with generalized periodontitis (AS-P). Patient demographic and periodontal characteristics (plaque index, bleeding on probing, probing pocket depth and clinical attachment loss), were collected. Patient whole blood and saliva levels of miR-155 and pro-inflammatory cytokine (interleukin-1ß), were quantified by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). One-way ANOVA with post-hoc Tukey test was used to determine differences among the four groups. Chi Square test was used for participant gender comparisons. Pearson correlation tests and multiple linear regression analyses were used to assess associations between the demographic and clinical variables analysed, versus IL-1ß and miR-155 levels. miR-155 and IL-1ß accuracy in differentiating healthy versus other patient groups were analysed using receiver operating characteristic (ROC) curves, by calculating area under the curve (AUC) values and sensitivity and specificity cut-off points using Youden's index. Statistical tests of sensitivity and specificity were conducted using the McNemar test. RESULTS: Whole blood miR-155 levels were elevated in periodontitis/non-periodontitis patients with CHD (AS-P, AS-C), and periodontitis patients alone (P) (p < 0.001). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses confirmed miR-155 accuracy in discriminating P, AS-C and AS-P groups (AUC 0.6861-0.9944, p < 0.0001-0.05), coupled with high sensitivity (76.7-100.0%), specificity (53.3-96.7%) and cut-off points (> 0.955- > 2.915 a.u.; p < 0.0001). miR-155 levels further distinguished between CHD (AS-C, AS-P) and periodontitis (P) patients (AUC ≥ 0.8378, sensitivity ≥ 88.7%, specificity ≥ 73.3%, cut-off > 2.82 a.u; p < 0.0001), and between AS-C and AS-P patients (AUC 0.7578, sensitivity 80.0%, specificity 50.0%, cut-off > 7.065 a.u; p < 0.001). Subsequent analyses identified positive correlations between miR-155 and the various patient demographics, salivary interleukin-1ß and periodontal parameters assessed. CONCLUSIONS: This study advocates miR-155 as an accurate diagnostic/prognostic biomarker of periodontitis and/or CHD severity, thereby improving detection and treatment for both conditions.

[Research Progress of microRNA-7/124/155 in Parkinson's Disease].

Parkinson's disease(PD)is the second most common neurodegenerative disease after Alzheimer's disease,with high morbidity and high disability rate.Since the early symptoms of PD are not typical and often similar to those of normal aging or other diseases.It is easy to missed diagnosis and misdiagnosis,which seriously affects the diagnosis and treatment of this disease and aggravetes the burden on the patients' life.MicroRNAs(miRNA)are a class of endogenous non-coding RNAs that are involved in post-transcriptional regulation by binding to target messenger RNAs(mRNA).They are highly conserved,short,easy to obtain,and can stably exist in peripheral body fluids.They have been used as biomarkers for a variety of diseases.Recent studies have demonstrated that miRNA play an important role in the development of PD.This paper reviews the recent research progress of miR-7/124/155,three mature miRNA in PD,aiming to provide reference for clarifying the pathogenesis and guiding the diagnosis and treatment of PD.

miR155 deficiency reduces breast tumor burden in the MMTV-PyMT mouse model.

miRNA155 (miR155) has emerged as an important regulator of breast cancer (BrCa) development. Studies have consistently noted an increase in miR155 levels in serum and/or tissues in patients with BrCa. However, what is less clear is whether this increase in miR155 is a reflection of oncogenic or tumor suppressive properties. To study the effects of miR155 in a transgenic model of BrCA, we developed an MMTV-PyMT mouse deficient in miR155 (miR155-/- PyMT). miR155-/- mice (n = 11) exhibited reduced tumor number and volume palpations at ∼14-18 wk of age compared with miR155 sufficient littermates (n = 12). At 19 wk, mammary glands were excised from tumors for RT-PCR, and tumors were counted, measured, and weighed. miR155-/- PyMT mice exhibited reduced tumor volume, number, and weight, which was confirmed by histopathological analysis. There was an increase in apoptosis with miR155 deficiency and a decrease in proliferation. As expected, miR155 deficiency resulted in upregulated gene expression of suppressor of cytokine signaling 1 (Socs1)-its direct target. There was a reduction in gene expression of macrophage markers (CD68, Adgre1, Itgax, Mrc1) with miR-155-/- and this was confirmed with immunofluorescence staining for F4/80. miR155-/- increased expression of M1 macrophage marker Nos2 and reduced expression of M2 macrophage markers IL-10, IL-4, Arg1, and MMP9. Overall, miR155 deficiency reduced BrCA and improved the tumor microenvironment through the reduction of genes associated with protumorigenic processes. However, given the inconsistencies in the literature, additional studies are needed before any attempts are made to harness miR155 as a potential oncogenic or tumor suppressive miRNA.NEW & NOTEWORTHY To examine the effects of miR155 in a transgenic model of breast cancer, we developed an MMTV-PyMT mouse-deficient in miR155. We demonstrate that global loss of miR155 resulted in blunted tumor growth through modulating the tumor microenvironment. Specifically, miR155-deficient mice had smaller and less invasive tumors, an increase in apoptosis and a decrease in proliferation, a reduction in tumor-associated macrophages, and the expression of genes associated with protumoral processes.

miR-155-5p in the spinal cord regulates hypersensitivity in a rat model of bone cancer pain.

BACKGROUND: Noncoding microRNAs have emerged as critical players of gene expression in the nervous system, where they contribute to regulating nervous disease. As stated in previous research, the miR-155-5p upregulation happens in the spinal cord at the nociceptive state. It was unclear if miR-155-5p is linked to bone cancer pain (BCP). Herein, we aimed at investigating the miR-155-5p functional regulatory function in BCP process and delineating the underlying mechanism. METHODS: The miRNA-155-5p levels and cellular distribution were determined by RNA sequencing, fluorescent in situ hybridization (FISH), and quantitative real-time PCR (qPCR). Immunoblotting, qPCR, dual-luciferase reporter gene assays, immunofluorescence, recombinant overexpression adeno-associated virus, small interfering RNA, intraspinal administration, and behavioral tests were utilized for exploring the downstream signaling pathway. RESULTS: The miR-155-5p high expression in spinal neurons contributes to BCP maintenance. The miR-155-5p blockage via the intrathecal injection of miR-155-5p antagomir alleviated the pain behavior; in contrast, upregulating miR-155-5p by agomir induced pain hypersensitivity. The miR-155-5p bounds directly to TCF4 mRNA's 3' UTR. BCP significantly reduced protein expression of TCF4 versus the Sham group. The miR-155-5p inhibition relieved the spinal TCF4 protein's down-expression level, while miR-155-5p upregulation by miR-155-5p agomir intrathecal injection decreased TCF4 protein expression in naïve rats. Additionally, TCF4 overexpression in BCP rats could increase Kv1.1. Moreover, TCF4 knockdown inhibited Kv1.1 expression in BCP rats. Indeed, TCF4 and Kv1.1 were co-expressed in BCP spinal cord neurons. CONCLUSION: The study findings stated the miR-155-5p pivotal role in regulating BCP by directly targeting TCF4 in spinal neurons and suggested that miR-155-5p could be a promising target in treating BCP.

IL-32 promotes the occurrence of atopic dermatitis by activating the JAK1/microRNA-155 axis.

BACKGROUND: This study aims to explore the mechanism of interleukin-32 (IL-32) affecting atopic dermatitis (AD) through the Janus-activated kinase-1 (JAK1)/microRNA-155 (miR-155) axis. METHODS: In this study, skin tissue samples and blood samples from normal subjects and patients with AD, human immortalized keratinocytes (HaCaT), and PA-induced mouse models of AD were selected for expression determination of IL-32, JAK1 and miR-155. The interaction among IL-32, JAK1 and miR-155 was identified with their roles in AD analyzed through loss- and gain-of-function assays. RESULTS: Elevated IL-32 was detected in AD tissues and blood samples and promoted the occurrence of AD. IL-32 upregulated JAK1 expression and phosphorylation of its downstream genes, thus activating the JAK signaling pathway. JAK1 promoted the expression of miR-155. IL-32/JAK1/miR-155 axis promoted inflammation in the AD skin reconstruction model. In vivo experiments further confirmed that IL-32 promoted AD development by activating the JAK1/miR-155 axis. CONCLUSION: The present study underlined that IL-32 promoted the occurrence of AD by promoting JAK1 expression to upregulate miR-155 expression.

microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82.

OBJECTIVE: Exosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82). METHODS: miR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model. RESULTS: miR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis. CONCLUSION: The study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.

PCB153 suppressed autophagy via PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling by the upregulation of microRNA-155 in rat primary chondrocytes.

Polychlorinated biphenyls (PCBs) are a typical type of persistent organic pollutant. PCB exposure is associated to the occurrence and development of osteoarthritis (OA); however, the involved mechanisms have yet to be elucidated. Here, we investigated the pro-osteoarthritic effect of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB153), and the involvement of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) and the RICTOR/Akt/mTOR signaling pathways. PCB153 of 20 and 30 µM increased the expression of MMP13 and decreased the expression of type II collagen, in a concentration-dependent manner. PCB153 treatment reduced the expression of Beclin 1 and LC3B, but increased the expression of p62 by upregulating miR-155 levels. PCB153 treatment activated the PI3K/Akt/mTOR signaling pathway by upregulating miR-155 levels. RICTOR was involved in activating the Akt/mTOR signaling pathway, and was also regulated by miR-155. In conclusion, PCB153 could promote the degradation of the extracellular matrix of chondrocytes by upregulating miR-155 via a mechanism related to the activation of the PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling pathway, which suppressed autophagy and facilitated the development of OA. MiR-155 may represent potential therapeutic targets to alleviate the development of OA.

Mesenchymal Stem Cell-Derived Exosomes Loaded with miR-155 Inhibitor Ameliorate Diabetic Wound Healing.

Diabetic wounds are one of the debilitating complications that affect up to 20% of diabetic patients. Despite the advent of extensive therapies, the recovery rate is unsatisfactory, and approximately, 25% of patients undergo amputation, thereby demanding alternative therapeutic strategies. On the basis of the individual therapeutic roles of the miR-155 inhibitor and mesenchymal stem cells (MSC)-derived exosomes, we conjectured that the combination of the miR-155 inhibitor and MSC-derived exosomes would have synergy in diabetic wound healing. Herein, miR-155-inhibitor-loaded MSC-derived exosomes showed synergistic effects in keratinocyte migration, restoration of FGF-7 levels, and anti-inflammatory action, leading to accelerated wound healing mediated by negative regulation of miR-155, using an in vitro co-culture model and in vivo mouse model of the diabetic wound. Furthermore, treatment with miR-155-inhibitor-loaded MSC-derived exosomes led to enhanced collagen deposition, angiogenesis, and re-epithelialization in diabetic wounds. This study revealed the therapeutic potential of miR-155-inhibitor-loaded MSC-derived exosomes in diabetic wound healing and opened the doors for encapsulating miRNAs along with antibiotics within the MSC-derived exosomes toward improved management of chronic, nonhealing diabetic wounds.

MicroRNA-155 expression is associated with pulpitis progression by targeting SHIP1.

BACKGROUND: Pulpitis is a commonly seen oral inflammation condition in clinical practice, it can cause much pain for the patient and may induce infections in other systems. Much is still unknown for the pathogenic mechanism of pulpitis. In this work, we discovered that the expression of miR-155 was associated with dental pulpal inflammation both in vivo and in vitro. METHODS AND RESULTS: Our experiments of LPS stimulated odontoblast cell line MDPC-23 showed miR-155 could act as a positive regulator by increasing the production of pro-inflammatory cytokines IL-1ß and IL-6 during inflammatory responses, whereas knockdown of miR-155 can reverse the effects. Bioinformatics analysis demonstrated that SHIP1 is a direct target of miR-155 in odontoblasts, this result was further verified at both mRNA and protein level. Inhibition of miR-155 resulted in the downregulation of inflammation factors, while co-transfection of si-SHIP1 and miR-155 inhibitor promoted the inflammatory responses. Treatment with miR-155 mimic or si-SHIP1 up-regulated the protein level of p-PI3K and p-AKT. By contrast, miR-155 inhibitor exerted the opposite effects. miR-155 mimics could upregulate the gene expression of IL-1ß and IL-6. Co-transfection of LY294002 and miR-155 mimic attenuated the inflammatory responses. Consistent with in vitro results, miR-155-/- mice could alleviate inflammatory response, as well as decrease the activation of p-PI3K and p-AKT, whereas increase the activation of SHIP1. CONCLUSIONS: Our data revealed a novel role for miR-155 in regulation of dental pulpal inflammatory response by targeting SHIP1 through PI3K/AKT signaling pathway.

MiR-155-5p modulates inflammatory phenotype of activated oral lichen-planus-associated-fibroblasts by targeting SOCS1.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines are closely associated with OLP development. In addition to immune cells, fibroblasts have been reported to induce regional inflammation. MicroRNA(miR)-155-5p is reportedly increased significantly in OLP and is known to regulate inflammation. This study aimed to investigate the role of miR-155-5p in fibroblasts of OLP lesions. METHODS AND RESULTS: Normal mucosal fibroblasts (NFs) and OLP associated-fibroblasts (OLP AFs) were isolated from the oral mucosa of 15 healthy controls and 30 OLP patients. We detected the expression of miR-155-5p and fibroblast activation protein alpha (FAP-α) using quantitative RT-PCR and analyzed their correlation. Interleukin (IL)-6 and IL-8 levels were determined using ELISA. Expression of suppressor of cytokine signaling (SOCS) 1 was analyzed by western blotting. A dual-luciferase reporter assay was performed to investigate the interaction between miR-155-5p and SOCS1. MiR-155-5p and FAP-α were significantly increased and positively correlated in OLP AFs. Overexpression of miR-155-5p in OLP AFs augmented IL-6 and IL-8 release and decreased SOCS1 expression, whereas knockdown of miR-155-5p in OLP AFs decreased IL-6 and IL-8 release. The expression of SOCS1 was downregulated in OLP AFs, and SOCS1 silencing augmented IL-6 and IL-8 production in OLP AFs. Furthermore, miR-155-5p inhibited SOCS1 expression by directly targeting its 3'-UTR in OLP AFs. CONCLUSIONS: MiR-155-5p regulates the secretion of IL-6 and IL-8 by downregulating the expression of SOCS1 in activated OLP AFs. Our results provide novel insights into the pathogenesis of OLP and identify a potential new target for OLP therapy.

MicroRNA-155-5p Targets NR3C2 to Promote Malignant Progression of Clear Cell Renal Cell Carcinoma.

BACKGROUND: The molecular heterogeneity of clear cell renal cell carcinoma (ccRCC) leads to a high mortality of the disease, which seriously threatens the life of patients. Therefore, this study explored the functional significance and mechanism of microRNA-155-5p and nuclear receptor subfamily 3 group C member 2 (NR3C2) in the regulation of ccRCC. METHODS: Expression levels of microRNA-155-5p and NR3C2 mRNA in ccRCC cells were analyzed by qRT-PCR, and the protein expression of NR3C2 in human ccRCC cells was measured by Western blot. Biological functions were determined through a series of in vitro experiments. The interaction between microRNA-155-5p and NR3C2 was tested by luciferase reporter gene assay. In addition, the effect of overexpressed or silenced microRNA-155-5p on cell phenotypes was evaluated in ccRCC cells. RESULTS: Experimental data suggested that overexpression or silencing of microRNA-155-5p in ccRCC could boost or suppress cancer cell proliferation and other malignant behaviors. Rescue experiments revealed that microRNA-155-5p facilitated the proliferation, migration, and invasion and suppressed the apoptosis of ccRCC by directly inhibiting the expression of NR3C2. CONCLUSIONS: This is the first study to generate new insights into the role of microRNA-155-5p/NR3C2 interaction in promoting the process of ccRCC, and it is possible to bring a turning point for the treatment of ccRCC.

HBX suppresses PTEN to promote the malignant progression of hepatocellular carcinoma through mi-R155 activation.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common and fatal tumors in the world, ranking third in cancer-related mortality. Chronic HBV infection is one of the major risk factors for hepatocellular carcinoma in China, Korea, and Sub-Saharan Africa. The HBx protein encoded by the X gene of HBV is a broadly regulated protein involved in transcriptional activation, epigenetics, apoptosis, DNA repair, and other regulatory processes. This study aimed to investigate the mechanism of HBx regulation of miR-155 and PTEN (Phosphatase and tensin homolog deleted on chromosome ten) in HBV-HCC. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatocellular carcinoma and normal subjects. The analysis was divided into different subgroups according to HBV positivity or negativity. At the cellular level, the biological roles of HBX, microRNA-155 and PTEN on hepatocellular carcinoma cells and their regulatory relationships with each other were verified. RESULTS: MicroRNA-155 and PTEN expression in HBV-positive HCC liver cancer tissues were negatively correlated, and HBX and miR-155 expression were positively correlated; microRNA-155 could target and inhibit PTEN expression, thereby promoting hepatocellular carcinoma cell activity, inhibiting apoptosis, and promoting invasion and migration; HBX could upregulate microRNA-155 thereby inhibit PTEN to promote malignant transformation of hepatocellular carcinoma. CONCLUSIONS: HBX could promote malignant transformation of hepatocellular carcinoma cells by upregulating microRNA-155 expression and thereby inhibiting the PTEN/PI3K-AKT pathway. Blocking miR-155 expression could attenuate the proliferation-promoting and invasive effects of HBX.