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mir-155 promotes m6A modification of SOX2 mRNA through targeted regulation of HIF-1α and delays wound healing in diabetic foot ulcer in vitro models

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JOURNAL OF DIABETES INVESTIGATION 2025年第1期16卷 60-71页

作者： Peng, Jiarui Zhu, Hong Ruan, Bin Duan, Zhisheng Cao, Mei Third Peoples Hosp Yunnan Prov Dept Endocrinol Kunming Peoples R China Third Peoples Hosp Yunnan Prov Dept Occupat Dis Kunming Peoples R China

ObjectiveDiabetic foot ulcers (DFU) are one of the most destructive complications of diabetes mellitus. The aim of this study was to link mir-155 and SOX2 with DFU to explore the regulation of wound healing by DFU and its potential *** keratinocytes (HaCaT) were induced with advanced glycation end products (AGEs) to construct DFU models in vitro. AGE-induced HaCaT cells were subjected to CCK-8 assays, flow cytometry, and wound healing assays to evaluate cell proliferation, apoptosis, and migration capacity, respectively. RT-qPCR and Western blotting were used to determine gene and protein expression levels, respectively. N6-methyladenosine (M6A) levels in total RNA were assessed using an M6A methylation quantification *** results suggested that the inhibition of mir-155 promoted wound healing in an in vitro DFU model, while the knockdown of HIF-1 alpha reversed this process, and that HIF-1 alpha was a target protein of mir-155. In addition, knockdown of HIF-1 alpha promoted the m6A level of SOX2 mRNA, inhibited the expression of SOX2, and inhibited the activation of the EGFR/MEK/ERK signaling pathway, thus inhibiting the proliferation and migration of HaCaT cells and promoting the apoptosis of HaCaT cells, while overexpression of SOX2 reversed this effect. We also found that METTL3 knockdown had the opposite effect of HIF-1 alpha *** of mir-155 promoted the expression of HIF-1 alpha and attenuated the m6A modification of SOX2 mRNA, thereby promoting the expression of SOX2 and activating the downstream EGFR/MEK/ERK signaling pathway to promote wound healing in an in vitro DFU model.

关键词： Diabetic foot ulcer mir-155 SOX2

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Deficiency of mir-155 in leukemic B-cells results in cell cycle arrest and deregulation of mir155HG/TP53INP1/CDKN1A/CCND1 network

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ARCHIVES OF MEDICAL RESEARCH 2025年第3期56卷 103124-103124页

作者： Golovina, Elena Kokavec, Juraj Kazantsev, Dmitry Yurikova, Oxana Bajecny, Martin Savvulidi, Filipp Georgijevic Simersky, Radim Lenobel, Rene Tost, Jorg Herynek, Vit Sefc, Ludek Sebela, Marek Klener, Pavel Zemanova, Zuzana Stopka, Tomas Vargova, Karina Savvulidi Charles Univ Prague Inst Pathol Physiol Fac Med 1 Nemocnice 5 Prague 12853 Czech Republic Charles Univ Prague Ctr Acad Sci Biotechnol & Biomed Vestec Czech Republic Charles Univ Prague Fac Med 1 Vestec Czech Republic Al Farabi Kazakh Natl Univ Alma Ata 480012 Kazakhstan Charles Univ Prague Fac Med 1 Ctr Adv Preclin Imaging Prague Czech Republic Czech Univ Fac Agrobiol & Food & Nat Resources Dept Anim Sci Prague Czech Republic Palacky Univ Fac Sci Dept Chem Biol Olomouc Czech Republic Czech Acad Sci Inst Expt Bot Lab Growth Regulators Olomouc 78371 Czech Republic Palacky Univ Olomouc Czech Republic Univ Paris Saclay Inst Biol Francois Jacob Ctr Natl Rech Genom Humaine CNRGH CEA Evry France Palacky Univ Fac Sci Dept Biochem Olomouc Czech Republic Gen Univ Hosp Charles Univ Inst Med Biochem & Lab Diagnost Fac Med 1 Prague Czech Republic

Background. Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (mirNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic mirNA-hsa-mir-155-5p (mir-155, mir155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how mir-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. Methods. We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the mir155HG gene. To describe changes at the transcriptome and mirNome level in mir-155-deficient cells, we performed mRNA-seq/mirNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. Results. The limited but phenotypically robust mir-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 ( CCND1 ). We confirmed the overexpression of canonical mir-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets ( FCRL5, ISG15, and MX1). Conclusions. We demonstrate that mir-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and mirNome via deregulation of the mir155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate mirNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of Instituto Mexicano del Seguro Social (IMSS). This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/)

关键词： mir-155 CRISPR/Cas9 Cell cycle B-cells Leukemia

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Blunt snout bream (Megalobrama amblycephala) circRXRBB regulates antimicrobial immune response against Aeromonas hydrophila infection via mir-155/socs1a axis

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AQUACULTURE 2025年 597卷

作者： Zhai, Wenya Lin, Junzhao Gao, Zexia Wang, Huanling Liu, Hong Huazhong Agr Univ Coll Fisheries Key Lab Freshwater Anim Breeding Key Lab Agr Anim Genet Breeding & ReprodMinist Ag Wuhan 430070 Peoples R China Minist Educ Engn Res Ctr Green Dev Convent Aquat Biol Ind Yang Wuhan 430070 Peoples R China

Circular RNAs (circRNAs) play an important role in various of human diseases by acting as competing endogenous RNAs (ceRNAs) and can serve as biomarkers and therapeutic targets. Our prior research has demonstrated that the circRNA-mirNA-mRNA regulatory network plays an important role in blunt snout bream (Megalobrama amblycephala) resistance to Aeromonas hydrophila infection. However, the exact regulatory mechanisms still need to be further explored. In this research, we identified a circRNA called circRXRBB that was down regulated following A. hydrophila challenge, suggesting its possible involvement in antimicrobial immune. Subsequently, the present study demonstrated that circRXRBB overexpression suppressed the expression levels of proinflammatory factors (il-6, il-1 beta, tnf-alpha, and ifn-gamma). Dual luciferase assay demonstrated that circRXRBB could directly adsorb mir-155 through sponge action, while mir-155 mimic could restore the inhibitory effect on inflammatory factors caused by circRXRBB overexpression. In addition, mir-155 can target socs1a, and the mir155/socs1a axis is one of the important pathways for circRXRBB to regulate immune response. In conclusion, this research demonstrated that circRXRBB is critical in regulating the antibacterial defense against A. hydrophila infection, which contributes to a better understanding of the ceRNA regulatory network and offers a foundation for future strategies in fish disease diagnose, prevention, and treatment.

关键词： circRXRBB mir-155 Socs1a ceRNA Innate immunity

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DJ-1 regulates astrocyte activation through mir-155/SHP-1 signaling in cerebral ischemia/reperfusion injury

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JOURNAL OF NEUROCHEMISTRY 2025年第1期169卷 e16230页

作者： Xue, Ying Wang, Yuan Chen, Tianyi Peng, Li Wang, Chenglong Xue, Guijun Yu, Shanshan Chongqing Med Univ Dept Pathol Yixueyuan Rd 1 Chongqing 400016 Peoples R China Chengdu Qingbaijiang Dist Peoples Hosp Dept Dermatol Chengdu Peoples R China Chongqing Med Univ Mol Med Diagnost & Testing Ctr Chongqing Peoples R China Chongqing Med Univ Affiliated Hosp 1 Dept Pathol Chongqing Peoples R China Chongqing Hosp Tradit Chinese Med Dept Pathol Chongqing Peoples R China Sichuan Univ West China Hosp Chengdu Peoples R China

Reactive astrocyte activation in the context of cerebral ischemia/reperfusion (I/R) injury gives rise to two distinct subtypes: the neurotoxic A1 type and the neuroprotective A2 type. DJ-1 (Parkinson disease protein 7, PARK7), originally identified as a Parkinson's disease-associated protein, is a multifunctional anti-oxidative stress protein with molecular chaperone and signaling functions. SHP-1 (Src homology 2 domain-containing phosphatase-1) is a protein tyrosine phosphatase closely associated with cellular signal transduction. mir-155 is a microRNA that participates in cellular functions by regulating gene expression. Recent studies have uncovered the relationship between DJ-1 and astrocyte-mediated neuroprotection, which may be related to its antioxidant properties and regulation of signaling molecules such as SHP-1. Furthermore, mir-155 may exert its effects by influencing SHP-1, providing a potential perspective for understanding the molecular mechanisms of stroke. A middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen-glucose deprivation/reperfusion (OGD/R) model were established to simulate focal cerebral I/R injury in vivo and in vitro, respectively. The in vivo interaction between DJ-1 and SHP-1 has been experimentally validated through immunoprecipitation. Overexpression of DJ-1 attenuates I/R injury and suppresses mir-155 expression. In addition, inhibition of mir-155 upregulates SHP-1 expression and modulates astrocyte activation phenotype. These findings suggest that DJ-1 mediates astrocyte activation via the mir-155/SHP-1 pathway, playing a pivotal role in the pathogenesis of cerebral ischemia-reperfusion injury. Our results provide a potential way for exploring the pathogenesis of ischemic stroke and present promising targets for pharmacological intervention.

关键词： astrocyte activation cerebral ischemia-reperfusion injury DJ-1 mir-155 SHP-1

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Combined replacement of lnc-MEG3 and mir-155 elicit tumor suppression in multiple myeloma

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EPIGENOMICS 2025年第3期17卷 167-177页

作者： El-Khazragy, Nashwa Abdelrahman, Sara Elsayed Darwish, Amal Hemida, Eman H. A. Ain Shams Univ Dept Clin Pathol Hematol 38 Abbassia SqNext to the Al Nour Mosque Cairo 11566 Egypt Ain Shams Univ Ain Shams Med Res Inst MASRI Fac Med 38 Abbassia SqNext to the Al Nour Mosque Cairo 11566 Egypt Ain Shams Univ Fac Med Dept Med Biochem & Mol Biol Cairo Egypt Ain Shams Univ Fac Sci Dept Biochem Cairo Egypt

AimsTo investigate the biological impact of simultaneous overexpression of lncRNA MEG3 and mir-155, termed a "double hit," on multiple myeloma (MM) cells compared to individual biomarker *** and methodsHuman MM cells were transfected with MEG3-overexpressed plasmids and mir-155 mimics. Cell cytotoxicity, apoptosis, and gene expression were evaluated in transfected cells and clinical ***3 and mir-155 were significantly downregulated in MM patients, with lower expression levels correlating with advanced disease stages and poorer survival. Dual overexpression induced potent cytotoxic effects in MM ***3 and mir-155 are potential tumor suppressors in MM. Simultaneous overexpression of both biomarkers could represent a novel therapeutic strategy, and their levels could serve as diagnostic and prognostic markers.

关键词： MEG3 mir-155 multiple myeloma prognostic factors therapeutic targets

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Increased circulating mir-155 identifies a subtype of preeclamptic patients

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BMC PREGNANCY AND CHILDBIRTH 2025年第1期25卷 1-11页

作者： Wang, Zhiyin Zheng, Mingming Duan, Honglei Wang, Yuan Dai, Yimin Tang, Huirong Wang, Ya Liu, Dan Cao, Chenrui Gu, Ning Weng, Qiao Zhou, Yan Zhao, Guangfeng Hu, Yali Nanjing Univ Nanjing Drum Tower Hosp Affiliated Hosp Med Sch Ctr Obstet & GynecolDept Obstet & Gynecol 321 Zhongshan Rd Nanjing 210008 Peoples R China Univ Calif San Francisco Dept Obstet Gynecol & Reprod Sci San Francisco CA 94143 USA

Introduction Preeclampsia is a common and severe pregnancy complication. The syndrome is highly heterogeneous, making accurate classification difficult, which is not conductive to find ways to predict and prevent this syndrome. Recently, we reported that high placental mir-155 defined a new subtype of preeclampsia. Here, we aimed to examine whether high maternal sero-mir-155 could be a marker to identify this subtype. Methods To explore whether the patients with high sero-mir-155 no matter in first and third trimester, we conducted a case-control and a longitudinal cohort study. We measured the sero-mir-155 levels at first, second and third trimesters in all pregnant women. Then, using the 95th percentile (P95) of sero-mir-155 in controls as the cut-off value, we divided the preeclamptic patients into high sero-mir-155 group (>= P95) and normal sero-mir-155 group (< P95). We compared the difference of clinical manifestations between two groups and used t-distributed stochastic neighbor embedding (t-SNE) to evaluate whether the patients with high sero-mir-155 could be clustered as a subtype. Finally, we evaluated the predictive value of sero-mir-155 in the subtype. Results The case-control study included 525 subjects (350 controls and 175 preeclampsia) and the longitudinal cohort study included 411 subjects (274 controls and 137 preeclampsia). Sero-mir-155 was significantly elevated in preeclampsia. Compared with preeclamptic patients with normal sero-mir-155 levels, the cases with high sero-mir-155 had significantly higher blood pressure and other severe preeclampsia-related complications. The incidences of HELLP syndrome [5.2% (5/96) vs. 0.9% (2/216), p < 0.01], visual disturbance [15.6% (15/96) vs. 4.6% (10/216), p < 0.01], hypertensive retinopathy [13.5% (13/96) vs. 3.2% (7/216), p < 0.01], and placenta abruption [7.3% (7/96) vs. 0.9% (2/216), p < 0.01] in patients with high mir-155 level were significantly increased. T-SNE analysis showed the patients with high

关键词： Preeclampsia Heterogeneous mir-155 Serum Subtype

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Evaluation of the Immunoadjuvant Effects of mir-155-Chitosan Polyplex on Leishmania major Infected Mice

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IMMUNOLOGICAL INVESTIGATIONS 2025年第2期54卷 217-233页

作者： Ardekan, Azam Pourabbasi Haghighi, Ali Mohammadi-Yeganeh, Samira Ghorbani-Bidkorpeh, Fatemeh Kashefi, Sarvenaz Koochaki, Ameneh Movahedi, Sara Rahmani, Yasamin Dastenaei, Ali Najafi Hoseini, Mostafa Haji Molla Shahid Beheshti Univ Med Sci Sch Med Dept Parasitol Tehran Iran Shahid Beheshti Univ Med Sci Med Nanotechnol & Tissue Engn Res Ctr Tehran Iran Shahid Beheshti Univ Med Sci Sch Adv Technol Med Dept Med Biotechnol Tehran Iran Shahid Beheshti Univ Med Sci Sch Pharm Dept Pharmaceut & Pharmaceut Nanotechnol Tehran Iran Shahid Beheshti Univ Med Sci Sch Med Dept Immunol Tehran *** Iran Pasteur Inst Iran Dept Immunol Tehran Iran

BackgroundMicroRNAs have gained attention as key immunomodulators, with mir-155 specifically shown in various studies to drive macrophage polarization toward the classical phenotype. This polarization is crucial, as classical macrophages play a well-recognized role in differentiating type-1 immune responses and resisting Leishmania *** present study aims to evaluate the anti-leishmanial immunoadjuvant effects of the mir-155 chitosan polyplex (mir-155 CP).MethodsThe anti-leishmanial immunoadjuvant activity of mir-155 CP synthesized by the coacervation method was assessed against L. major (MRHO/IR/75/ER) by analyzing the infectivity rate on RAW 264.7 cells in ***-155 CP as an adjuvant co-administrated with soluble Leishmania antigen (SLA) for immunization of BALB/c mice, then the challenge was performed by subcutaneous injection of 1 x 106 L. major promastigotes. Eight weeks following the challenge, lesion size, parasite load, cytokine assay, and nitric oxide production were *** nanoparticles were produced with a size of 233.87 +/- 8 nm and a zeta potential of + 22.6 +/- 2 mV with good transfection efficiency. The mean infection index among pretreated cells with mir-155 CP (72 +/- 1.1) decreased significantly compared to the control group (420 +/- 2.8). The parasite burden and the size of the lesions were significantly reduced in the immunized infected mice. Vaccination by mir-155 CP/SLA triggered the production of IFN-gamma and NO and changed the cytokine profile of antigen-specific ***:The effectiveness of the SLA vaccine can be enhanced by including mir-155 CP as an adjuvant. SLA and mir-155 CP co-administration improve the type-1 immune response. This enhanced immune response helps prevent severe leishmaniasis.

关键词： Adjuvant chitosan Leishmania major mir-155 vaccine

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Negative pressure wound therapy promotes wound healing by down-regulating mir-155 expression in granulation tissue of diabetic foot ulcers

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SCIENTIFIC REPORTS 2025年第1期15卷 1-13页

作者： Huang, Yixuan Yu, Zhenyi Xu, Murong Zhao, Xiaotong Tang, Yizhong Luo, Li Deng, Datong Chen, Mingwei Anhui Med Univ Affiliated Hosp 1 Dept Endocrinol 218 Jixi Rd Hefei 230032 Anhui Peoples R China Anhui Med Univ Affiliated Hosp 1 Dept Burn Hefei 230032 Anhui Peoples R China

Our study aims to investigate the effect of negative pressure wound therapy (NPWT) on microRNA-155 (mir-155) in the granulation tissue of patients suffering from diabetic foot ulcers (DFUs) and its correlation with wound healing. A total of sixty patients diagnosed with DFUs were randomly assigned to either the NPWT group (n = 40) or the Non-NPWT group (n = 20) in a 2:1 ratio. After debridement, the NPWT group received NPWT treatment for one week, while the Non-NPWT group underwent routine dressing therapy. The expression of mir-155 in DFU granulation tissues was evaluated by qRT-PCR before and after treatment for one week. Following termination, wound healing rates were assessed in the NPWT group, and the correlation between variations in mir-155 expression (Delta mir-155) and wound healing was analyzed pre and post NPWT treatment. In vitro experiments were conducted to investigate the effects of negative pressure on variations of mir-155 expression, as well as proliferation, migration, and apoptosis in normal human dermal fibroblasts (NHDFs). The NPWT group showed a decrease in mir-155 expression in wound granulation tissue compared with pre-treatment [4.12 (1.22, 14.85) vs. 6.83 (2.15, 15.72), P < 0.05]. Conversely, there was no statistically significant difference in mir-155 expression in wound granulation tissue between pre-treatment and post-treatment in the Non-NPWT group (P > 0.05). However, analysis revealed a positive correlation between Delta mir-155 and wound healing rate after 4 weeks in the NPWT group (chi 2 = 4.829, P = 0.028). The in vitro experiments showed a significant decrease in mir-155 expression in NHDFs under negative pressure measured at -125 mmHg (P < 0.05). This reduction in mir-155 expression, in turn, enhanced the proliferation and migration ability while decreasing the apoptosis rate of NHDFs by targeting the upregulation of fibroblast growth factor 7 (FGF7) gene expression (P < 0.05). It is concluded that NPWT promotes DFU healing by r

关键词： Diabetic foot ulcer (DFU) Negative pressure wound therapy (NPWT) Normal human dermal fibroblasts (NHDFs) MicroRNA mir-155

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Overexpression of mir-155 Modulates Interferon Response and Inhibits Viral Replication of IHNV and IPNV in EPC Cells

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JOURNAL OF FISH DISEASES 2025年第5期48卷 e14092页

作者： Abdellaoui, Najib Park, Ik-Jun Choi, Subin Kim, Minji Kim, Min Sun Kongju Natl Univ Dept Biol Sci Gongju South Korea

Infections caused by RNA viruses, including infectious haematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV), result in substantial economic losses in the aquaculture industry. MicroRNAs (mirNAs), particularly mir-155, play crucial roles in regulating host immune responses and viral infections. In this study, we investigated the overexpression effect of mir-155 in Epithelioma papulosum cyprini (EPC) cells infected with IHNV and IPNV and analysed the mechanisms underlying these antiviral activities. EPC cells were transfected with mir-155 at 40 pmol and then infected with IHNV or IPNV at an MOI of 0.01. The cytopathogenic effect (CPE) was observed for 5 days post-infection. The cells transfected with mir-155 did not show any signs of CPE or exhibit any viral growth over time after infection with both viruses. Additionally, real-time qPCR of type I interferon-related immune genes (ISG15 and Mx1) showed upregulation at 0, 24, and 48 h.p.i in cells transfected with mir-155. At 48 h post-infection, the cells transfected with mir-155 did not show any bands of viral protein by western blot. Furthermore, the overexpression of mir-155 in EPC cells significantly enhanced the expression of interferon response genes by targeting BCL2 and CYLD and suppressed the viral replication through directly targeting viral genes, including the L gene of IHNV and the VP2 gene of IPNV. These findings elucidate the dual mechanism of mir-155's antiviral effect through immune modulation and direct viral gene targeting, offering insights for developing novel antiviral strategies in aquaculture.

关键词： immunity modulation mir-155 RNA virus viral genes

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The role of mir-155 in cardiovascular diseases: Potential diagnostic and therapeutic targets

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INTERNATIONAL JOURNAL OF CARDIOLOGY CARDIOVASCULAR RISK AND PREVENTION 2025年 24卷 200355-200355页

作者： Zhang, Rui-Lin Wang, Wei-Ming Li, Ji-Qiang Li, Run-Wen Zhang, Jie Wu, Ya Liu, Yong Southwest Med Univ Affiliated Hosp Dept Vasc Surg Luzhou 646000 Peoples R China Southwest Med Univ Metab Vasc Dis Key Lab Sichuan Prov Affiliated Hosp Luzhou 646000 Peoples R China Southwest Med Univ Key Lab Med Electrophysiol Minist Educ Luzhou 646000 Peoples R China Southwest Med Univ Collaborat Innovat Ctr Prevent Cardiovasc Dis Med Electrophysiol Key Lab Sichuan Prov Inst Cardiovasc Res Luzhou 646000 Peoples R China Southwest Med Univ Affiliated Hosp Dept Gen Surg Luzhou 646000 Peoples R China 25 Taiping St Luzhou Sichuan Peoples R China

Cardiovascular diseases (CVDs), such as atherosclerotic cardiovascular diseases, heart failure (HF), and acute coronary syndrome, represent a significant threat to global health and impose considerable socioeconomic burdens. The intricate pathogenesis of CVD involves various regulatory mechanisms, among which microRNAs (mirNAs) have emerged as critical posttranscriptional regulators. In particular, mir-155 has demonstrated differential expression patterns across a spectrum of CVD and is implicated in the etiology and progression of arterial disorders. This systematic review synthesizes current evidence on the multifaceted roles of mir-155 in the modulation of genes and pathological processes associated with CVD. We delineate the potential of mir-155 as a diagnostic biomarker and therapeutic target, highlighting its significant regulatory influence on conditions such as atherosclerosis, aneurysm, hypertension, HF, myocardial hypertrophy, and oxidative stress. Our analysis underscores the transformative potential of mir-155 as a target for intervention in cardiovascular medicine, warranting further investigation into its clinical applicability.

关键词： MicroRNA mir-155 Cardiovascular diseases Potential diagnostic Therapeutic target

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