We have previously found that the DAPK-DDX20 signaling axis exerts an anti-cancer activity in hepatocellular carcinoma (HCC) by inhibiting the GTPase activity of CDC42, thereby reducing the invasive and migratory capabilities of cancer cells without affecting cell proliferation. DDX20 serves as an intermediate protein regulated by DAPK in the control of CDC42. Specifically, DAPK enhances DDX20 protein levels by suppressing DDX20 degradation. However, the mechanism underlying DAPK regulation of DDX20 remains unclear. In the current study, we discovered that DDX20 is degraded through the ubiquitin-proteasome pathway and identified TRIM25 as the E3 ubiquitin ligase of DDX20. TRIM25 mediates the proteasomal degradation of DDX20 by binding to, and ubiquitinating the 1-244 amino acid region of DDX20. Moreover, DAPK interacts with this 1-244 segment of DDX20, inhibiting its ubiquitination and enhancing its stability, despite the lack of direct physical interaction between DAPK and the 1-244 region of DDX20. Remarkably, DAPK, TRIM25, and DDX20 form a ternary protein complex in cells, and knockdown of TRIM25 leads to a reduction in the cellular levels of the binary DAPK-DDX20 complex, suggesting that TRIM25 acts as an important intermediate protein linking DAPK and DDX20. TRIM25 functions as an oncogene in liver cancer, as shRNA-mediated silencing of TRIM25 inhibits cell migration and invasion. Therefore, these novel findings of the interaction among these three proteins not only enhances our knowledge of the downstream molecular network of DAPK and its possible role in the development of HCC, but also provides potential druggable targets for the future development of novel anticancer drug therapeutics.

Difficult-to-heal skin wounds are serious complications of diabetes. Microneedles (MNs) are a new type of physically penetrating wound dressing that can synergistically carry drugs. In this study, good biocompatible gelatin methacrylate (Gelma) and polyvinyl alcohol (PVA), loading with doxycycline hydrochloride (DH) and vascular endothelial growth factors (VEGF) are used to prepare the DH/VEGF@Gelma-MNs. Gelma-MNs possess well-aligned conical structures, good mechanical, and swelling properties, and could penetrate the skin. DH/VEGF@Gelma-MNs show biocompatibility and antibacterial ability to inhibit the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Besides, DH/VEGF@Gelma-MNs significantly promote the migration and tube formation of human umbilical vein endothelial cells (HUVECs). DH/VEGF@Gelma-PNs treatment accelerates diabetic wound closure in vivo compared to DH/VEGF@Gelma-plain patch (DH/VEGF@Gelma-PPs) flat patch and DH/VEGF solution injection. Histological evaluation shows that DH/VEGF@Gelma-MNs coverage presents intact wound re-epithelialization, follicle and sebaceous gland formation, more collagen deposition and remodeling, and angiogenesis. In conclusion, DH/VEGF@Gelma-MNs exert antimicrobial and angiogenic effects by releasing DH and VEGF to promote diabetic wound healing, posing an intriguing strategy based on a synergistic MN therapeutic platform. Gelatin methacrylate (Gelma) and polyvinyl alcohol (PVA), loading with doxycycline hydrochloride (DH) and vascular endothelial growth factors (VEGF) are used to prepare the DH/VEGF@Gelma-MNs, which show biocompatibility and antibacterial ability to inhibit S. aureus and E. coli growth. DH/VEGF@Gelma-MNs significantly promote the migration and tube formation of HUVECs, and accelerat diabetic wound closure. image

Breast cancer (BC) is one of the most common malignancies. However, the existing pathological grading system cannot accurately and effectively predict the survival rate and immune checkpoint treatment response of BC patients. In this study, based on The Cancer Genome Atlas (TCGA) database, a total of 7 immune-related genes (IRGs) were screened out to construct a prognostic model. Subsequently, the clinical prognosis, pathological characteristics, cancer-immunity cycle, tumour immune dysfunction and exclusion (TIDE) score, and immune checkpoint inhibitor (ICI) response were compared between the high- and low-risk groups. In addition, we determined the potential regulatory effect of NPR3 on BC cell proliferation, migration, and apoptosis. The model consisting of 7 IRGs was an independent prognostic factor. Patients with lower risk scores exhibited longer survival times. Moreover, the expression of NPR3 was increased but the expression of PD-1, PD-L1, and CTLA-4 was decreased in the high-risk group compared to the low-risk group. In addition, compared with si-NC, si-NPR3 suppressed proliferation and migration but promoted apoptosis in both MDA-MB-231 and MCF-7 cells. This study presents a model for predicting survival outcomes and provides a strategy to guide effective personalized immunotherapy in BC patients.

Background: Understanding the blood supply to the nipple-areola complex (NAC) in hypertrophic breasts is essential to reduce the risk of NAC necrosis during reduction mammaplasty. The aim of this study was to use dynamic contrast-enhanced magnetic reso-nance imaging (DCE-MRI) to determine the NAC blood supply of hypertrophic breasts compared with normal-sized breasts.Methods: DCE-MRI images of 100 Asian women (100 hypertrophic breasts and 100 normal-sized breasts) were included retrospectively. All vessels supplying the NAC were identified using axial, coronal, and sagittal maximum-intensity projection images. The diameter, length, and distance to the skin surface of source vessels were measured. Results: The number of source vessels in the hypertrophic breasts was larger than that in the normal-sized breasts. 97.0% of hypertrophic breasts had multizone blood supply to the NAC. In hypertrophic and normal-sized breasts, the proportion of vessels was highest in the supermedial zone, followed by the superolateral zone and central zone. The diameter of medial and lateral vessels was significantly increased in hypertrophic breasts. Besides, the length of source vessels in hypertrophic breasts was larger than that in normal-sized breasts.Conclusions: Hypertrophic breasts tend to have a richer blood supply to the NAC than normal -sized breasts. The predominant vessels supplying the NAC of hypertrophic breasts are the su-peromedial, followed by the superolateral and central.Level of Evidence: IV (c) 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by El-sevier Ltd. All rights reserved.

Ovarian cancer (OV) is an aggressive malignancy that poses a significant threat to the health and lives of women. Cuproptosis is a newly discovered form of programmed cell death that offers a promising therapeutic target, although its significance in cancer progression remains uncertain. In this study, we established a prognostic model of OV with six cuproptosis-related long non-coding RNAs (lncRNAs), including CTC.246B18.8, LINC00337, RP11.568N6.1, RP11.158I9.8, RP11.678G14.3 and CYP4F26P, based on the data of The Cancer Genome Atlas (TCGA). Lower risk scores were associated with favorable prognosis. In addition, a negative outcome was associated with high expression of CTC.246B18.8. According to the ESTIMATE algorithm, CTC.246B18.8 was negatively correlated with the ImmuneScore, and positively with immune checkpoints, immune cell infiltration, and tumor mutation burden (TMB). Moreover, gene set enrichment analysis (GSEA) revealed that pathways related to immunosuppression are likely activated in response to CTC-246B18.8 overexpression. Furthermore, CTC-246B18.8 expression was also associated with the sensitivity to various chemotherapy drugs. The expression patterns of the above lncRNAs were verified in ovarian tumor cell lines (SK-OV-3, COC1, and A2780) and normal ovarian epithelial cells (IOSE - 80). Six cuproptosis-related genes (CRGs), including ATP7B, MTF1, SLC31A1, DLD, ATP7A and DLAT, were differentially expressed between CTC-246B18.8high and CTC-246B18.8low patient groups, and exhibited organ-specific expression patterns pan-cancer. Small molecule drugs that target these CRGs were predicted, and potential candidates included DIAMIDE, bathocuproine disulfonate, D-penicillamine, etc. To summarize, our findings provide molecular insights into the role of cuproptosis in OV, and the signature lncRNAs and CRGs should be investigated further as immunotherapy biomarkers of OV.

BackgroundTumor-associated macrophages (TAMs) are the most abundant types of immune cells in the tumor microenvironment (TME) of breast cancer (BC). TAMs usually exhibit an M2 phenotype and promote tumor progression by facilitating immunosuppression. This study aimed to investigate the effect of CAA-derived IL-6 on macrophage polarization in promoting BC progression.MethodsHuman BC samples and adipocytes co-cultured with 4T1 BC cells were employed to explore the properties of CAAs. The co-implantation of adipocytes and 4T1 cells in mouse tumor-bearing model and tail vein pulmonary metastasis model were constructed to investigate the impact of CAAs on BC malignant progression in vivo. The functional assays, qRT-PCR, western blotting assay and ELISA assay were employed to explore the effect of CAA-derived IL-6 on macrophage polarization and programmed cell death protein ligand 1 (PD-L1) expression.ResultsCAAs were located at the invasive front of BC and possessed a de-differentiated fibroblast phenotype. CAAs facilitated the malignant behaviors of 4T1 cells in vitro, and promoted 4T1 tumor growth and pulmonary metastasis in vivo. The IHC staining of both human BC specimens and xenograft and the in vitro experiment indicated that CAAs could enhance infiltration of M2 macrophages in the TME of 4T1 BC. Furthermore, CAA-educated macrophages could enhance malignant behaviors of 4T1 cells in vitro. More importantly, CAAs could secret abundant IL-6 and thus induce M2 macrophage polarization by activating STAT3. In addition, CAAs could upregulate PD-L1 expression in macrophages.ConclusionsOur study revealed that CAAs and CAA-educated macrophages enhanced the malignant behaviors of BC. Specifically, CAA-derived IL-6 induced migration and M2 polarization of macrophages via activation STAT3 and promoted macrophage PD-L1 expression, thereby leading to BC progression.

Breast cancer (BC) ranks first in the incidence of tumors in women and remains the most prevalent malignancy in women worldwide. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) profoundly influence the progression, recurrence, and therapeutic resistance in BC. Here, we intended to establish a risk signature based on screened CAF-associated genes in BC (BCCGs) for patient stratification. Initially, BCCGs were screened by a combination of several CAF gene sets. The identified BCGGs were found to differ significantly in the overall survival (OS) of BC patients. Accordingly, we constructed a prognostic prediction signature of 5 BCCGs, which were independent prognostic factors associated with BC based on univariate and multivariate Cox regression. The risk model divided patients into low- and high-risk groups, accompanied by different OS, clinical features, and immune infiltration characteristics. Receiver operating characteristic (ROC) curves and a nomogram further validated the predictive performance of the prognostic model. Notably, 21 anticancer agents targeting these BCCGs possessed better sensitivity in BC patients. Meanwhile, the elevated expression of the majority of immune checkpoint genes suggested that the high-risk group may benefit more from immune checkpoint inhibitors (ICIs) therapy. Taken together, our well-established model is a robust instrument to precisely and comprehensively predict the prognosis, immune features, and drug sensitivity in BC patients, for combating BC.

Wound healing after skin injury is a dynamic and highly coordinated process involving a well-orchestrated series of phases, including hemostasis, inflammation, proliferation, and tissue remodeling. Epigenetic regulation refers to genome-wide molecular events, including DNA methylation, histone modification, and non-coding RNA regulation, represented by microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Epigenetic regulation is pervasively occurred in the genome and emerges as a new role in gene expression at the post-transcriptional level. Currently, it is well-recognized that epigenetic factors are determinants in regulating gene expression patterns, and may provide evolutionary mechanisms that influence the wound microenvironments and the entire healing course. Therefore, this review aims to comprehensively summarize the emerging roles and mechanisms of epigenetic remodeling in wound healing. Moreover, we also pose the challenges and future perspectives related to epigenetic modifications in wound healing, which would bring novel insights to accelerated wound healing.

八段锦为我国特有的导引术,防治郁证有独特的优势.基于传统医学理论,通过归纳总结相关文献,从八段锦对郁证的防与治及对人体八大系统的影响,分析八段锦的丰富内涵,提出八段锦作为治疗郁证的有效手段,可以改善心理健康状况,具有积极的社会价值.

BackgroundTumors in the central and nipple portion (TCNP) are associated with poor prognosis and aggressive clinicopathological characteristics. The availability and safety of postmastectomy reconstruction in breast cancer patients with TCNP have still not been deeply explored. It is necessary to investigate whether reconstruction is appropriate for TCNP compared with non-reconstruction therapy in terms of survival outcomes.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled TCNP patients diagnosed between the years 2010 and 2016. The propensity score matching (PSM) technique was applied to construct a matched sample consisting of pairs of non-reconstruction and reconstruction groups. Survival analysis was performed with the Kaplan–Meier method. Univariate and multivariate Cox proportional hazard models were applied to estimate the factors associated with breast cancer-specific survival (BCSS) and overall survival (OS).ResultsIn the overall cohort, a total of 6,002 patients were enrolled. The patients in the reconstruction group showed significantly better BCSS (log-rank, p < 0.01) and OS (log-rank, p < 0.01) than those in the non-reconstruction group (832 patients) after PSM. However, the multivariate Cox regression model revealed that breast reconstruction was not associated with worse BCSS and OS of TCNP patients.ConclusionOur study provided a new perspective showing that breast reconstruction did not affect the survival and disease prognosis in the cohort of TCNP patients from SEER databases, compared with non-reconstruction. This finding provides further survival evidence supporting the practice of postmastectomy reconstruction for suitable TCNP patients, especially those with a strong willingness for breast reconstruction.

咳嗽变异性哮喘是慢性咳嗽的主要病因,中医治疗咳嗽变异性哮喘疗效良好,但未形成统一的认识,肺胃相关理论对临床论治咳嗽变异性哮喘具有极重要的指导意义,现基于肺胃相关理论,整理近年来咳嗽变异性哮喘的中医诊治方法,探究咳嗽变异性哮喘的病因病机,根据其发病特点,提出此病的治疗大纲:发作期治以和降肺胃,祛痰化饮;缓解期治以扶正固本,补土生金.这为肺胃相关理论指导临床诊治咳嗽变异性哮喘和完善此病中医诊治大纲提供理论依据.

Background: Breast cancer (BC) is one of the most common cancers in women. The discovery of available biomarkers is crucial for early diagnosis and improving prognosis. The effect of POP1 in BC remains unrevealed. Our study aims to explore the expression of POP1 in BC and demonstrate its clinical significance and potential molecular mechanisms. Methods: The Cancer Genome Atlas (TCGA) BC cohort transcriptome data and corresponding clinical information were downloaded. GSE42568 cohort, GSE162228 cohort, GSE7904 cohort, and GSE161533 cohort in the Gene Expression Omnibus (GEO) database were used as verification groups. R software and several web tools were used for statistical analysis. Moreover, the proliferation, transwell, wound healing experiments, and flow cytometry were used for in vitro investigation. Results: Compared with normal breast tissue, POP1 expression was up-regulated in BC tissue with a higher mutation rate. POP1 had good diagnostic value for BC and could be utilized as a new marker. POP1 was significantly correlated with multiple pathways in BC and played an important role in the immune infiltration of BC. High-POP1 expression patients were more prone to be responded to immunotherapy and had a significantly higher percentage of immunotherapy response rate. Moreover, POP1 promoted proliferation and migration and inhibited apoptosis in BC cells. Conclusions: POP1 expression was up-regulated in BC and was associated with a poor prognosis. Patients with high-POP1 expression were more likely to be responded to immunotherapy. Our study can provide a potential marker POP1 for BC, which is beneficial in the diagnosis and treatment of BC.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is an uncommon type of T-cell lymphoma. Although with a low incidence, the epidemiological data raised the biosafety and health concerns of breast reconstruction and breast augmentation for BIA-ALCL. Emerging evidence confirms that genetic features, bacterial contamination, chronic inflammation, and textured breast implant are the relevant factors leading to the development of BIA-ALCL. Almost all reported cases with a medical history involve breast implants with a textured surface, which reflects the role of implant surface characteristics in BIA-ALCL. With this review, we expect to highlight the most significant features on etiology, pathogenesis, diagnosis, and therapy of BIA-ALCL, as well as we review the physical characteristics of breast implants and their potential pathogenic effect and hopefully provide a foundation for optimal choice of type of implant with minimal morbidity.

督灸是中医治未病思想的具体实施方式之一,具有安全性高、疗效显著的特性,在临床上得到广泛应用并引起国内外学者的关注.本文通过整理与督灸相关的历代文献,对督灸的历史源流、内涵和实际应用进行阐述,提出现阶段督灸在应用与研究中存在的问题,以期提高督灸临床治疗规范,为督灸科研提供新的方向.

Abstract Background Gastric mucosal lesions (GML) are common in gastric diseases and seriously affect the quality of life. There are inevitable side effects in drug therapy. Acupuncture is an important part of traditional Chinese medicine. Electro-acupuncture (EA) has unique curative effect in treatment of GML. However, there are still few reports on the central mechanism of electro-acupuncture in treatment of GML. In this study, NMR metabonomics was used to explore the central metabolic change mechanism of electro-acupuncture in treatment of GML. Methods SD rats were randomly divided into Control, GML and EA groups. According to different intervention time, each group was further divided into 3 subgroups. This study mainly established GML model rats by 75% ethanol. Dynamic expressions of metabolites in cerebral cortex and medulla were observed by 1D 1H Nuclear Magnetic Resonance (NMR) metabolomics, combined with gastric mucosal histopathological examination to evaluate the time-effect relationship of electro-acupuncture at Zusanli (ST36) and Liangmen (ST21) points for 1 day, 4 days and 7 days treatment of GML. Results The results showed that the repair effect of electro-acupuncture on gastric mucosal injury was the most obvious in 4 days and stable in 7 days, and 4 days electro-acupuncture can effectively inhibit GML gastric mucosal inflammation and the expression of inflammatory cells. Meanwhile, the NMR spectrum results of medulla and cerebral cortex showed that, 21 potential metabolites were identified to participate in the mechanism of pathogenesis of GML and the regulation of electro-acupuncture, including 15 in medulla and 10 in cerebral cortex. Metabolic pathway analysis showed that the differential metabolites involved 19 metabolic pathways, which could be divided into energy, neurotransmitters, cells and cell membrane and antioxidation according to their functions. The correlation analysis of stomach, medulla and cerebral cortex shows that the stimulation signal of GML may reach the cerebral cortex from the stomach through medulla, and electro-acupuncture can treat GML by regulating the central nervous system (CNS). Conclusions 4 days electro-acupuncture treatment can significantly improve gastric mucosal injury, and the curative effect tends to be stable in 7 days treatment. Meanwhile, the pathogenesis of GML and the efficacy of electro-acupuncture involve metabolic pathways such as energy, neurotransmitters, cells and antioxidation, and electro-acupuncture can treat GML by regulating CNS.

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

Background Lung adenocarcinoma (LUAD) is one of the most common types in the world with a high mortality rate. Despite advances in treatment strategies, the overall survival (OS) remains short. Our study aims to establish a reliable prognostic signature closely related to the survival of LUAD patients that can better predict prognosis and possibly help with individual monitoring of LUAD patients. Methods Raw RNA-sequencing data were obtained from Fudan University and used as a training group. Differentially expressed genes (DEGs) for the training group were screened. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate cox regression analysis were conducted to identify the candidate prognostic genes and construct the risk score model. Kaplan–Meier analysis, time-dependent receiver operating characteristic (ROC) curve were used to evaluate the prognostic power and performance of the signature. Moreover, The Cancer Genome Atlas (TCGA-LUAD) dataset was further used to validate the predictive ability of prognostic signature. Results A prognostic signature consisting of seven prognostic-related genes was constructed using the training group. The 7-gene prognostic signature significantly grouped patients in high and low-risk groups in terms of overall survival in the training cohort [hazard ratio, HR = 8.94, 95% confidence interval (95% CI)] [2.041–39.2]; P = 0.0004), and in the validation cohort (HR = 2.41, 95% CI [1.779–3.276]; P < 0.0001). Cox regression analysis (univariate and multivariate) demonstrated that the seven-gene signature is an independent prognostic biomarker for predicting the survival of LUAD patients. ROC curves revealed that the 7-gene prognostic signature achieved a good performance in training and validation groups (AUC = 0.91, AUC = 0.7 respectively) in predicting OS for LUAD patients. Furthermore, the stratified analysis of the signature showed another classification to predict the prognosis. Conclusion Our study suggested a new and reliable prognostic signature that has a significant implication in predicting overall survival for LUAD patients and may help with early diagnosis and making effective clinical decisions regarding potential individual treatment.

Breast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.

BACKGROUND:N6-methyladenosine (m6A), the most abundant and reversible modification of mRNAs in eukaryotes, plays pivotal role in breast cancer (BC) tumorigenesis and progression. Circular RNAs (circRNAs) can act as tumor promoters or suppressors by microRNA (miRNA) sponges in BC. However, the underlying mechanism of circRNAs in BC progression via regulating m6A modulators remains unclear.METHODS:Prognostic m6A RNA methylation regulators were identified in 1065 BC patients from The Cancer Genome Atlas (TCGA) project. Differentially expressed (DE) miRNAs and DE circRNAs were identified between BC and normal samples in TCGA and GSE101123, respectively. MiRNA-mRNA interactive pairs and circRNA-miRNA interactive pairs were verified by MiRDIP and Circular RNA Interactome. GSEA, KEGG, and ssGSEA were executed to explore the potential biological and immune functions between HNRNPC-high and HNRNPC-low expression groups. qRT-PCR and Western blot were used to quantify the expression of HNRNPC and circBACH2 in MCF-7 and MDA-MB-231 cells. The proliferation of BC cells was assessed by CCK-8 and EdU assay.RESULTS:2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients. Then, the regulatory network of circRNA-miRNA-m6A modulators was constructed, which consisted of 2 DE m6A modulators (HNRNPC and YTHDF3), 12 DE miRNAs, and 11 DE circRNAs. Notably, BC patients with high expression of HNRNPC and low expression of hsa-miR-944 were correlated with late clinical stages and shorter survival times. Besides, the results from the KEGG inferred that the DE HNRNPC was associated with the MAPK signaling pathway in BC. Moreover, the circBACH2 (hsa_circ_0001625) was confirmed to act as hsa-miR-944 sponge to stimulate HNRNPC expression to promote BC cell proliferation via MAPK signaling pathway, thus constructing a circBACH2/hsa-miR-944/HNRNPC axis in BC.CONCLUSIONS:Our findings decipher a novel circRNA-based m6A regulatory mechanism involved in BC progression, thus providing attractive diagnostic and therapeutic strategies for combating BC.

Obesity is associated with energy metabolic disturbance and is caused by long-term excessive energy storage in white adipose tissue (WAT). The WAT browning potentially reduces excessive energy accumulation, contributing an attractive target to combat obesity. As a pivotal regulator of cell growth, the transcription factor E2F1 activity dysregulation leads to metabolic complications. The regulatory effect and underlying mechanism of E2F1 knockout on WAT browning, have not been fully elucidated. To address this issue, in this study, the in vivo adipose morphology, mitochondria quantities, uncoupling protein 1 (UCP-1), autophagy-related genes in WAT of wild-type (WT) and E2F1(-/-) mice were detected. Furthermore, we evaluated the UCP-1, and autophagy-related gene expression in WT and E2F1(-/-) adipocyte in vitro. The results demonstrated that E2F1 knockout could increase mitochondria and UCP-1 expression in WAT through autophagy suppression in mice, thus promoting WAT browning. Besides, adipocytes lacking E2F1 showed upregulated UCP-1 and downregulated autophagy-related genes expression in vitro. These results verified that E2F1 knockout exerted effects on inducing mice WAT browning through autophagy inhibition in vivo and in vitro. These findings regarding the molecular mechanism of E2F1-modulated autophagy in controlling WAT plasticity, provide a novel insight into the functional network with the potential therapeutic application against obesity.