Background Ulcerative colitis (UC), a refractory subtype of inflammatory bowel disease (IBD), is clinically characterized by chronic abdominal pain and bloody hematochezia. Although therapeutic interventions have advanced significantly in recent years, existing treatment modalities remain limited. Akebia saponin D (ASD), a bioactive triterpenoid saponin extracted from the traditional medicinal herb Dipsacus asper, has been demonstrated potent multimodal bioactivity. Purpose This study systematically evaluates the therapeutic potential of ASD in UC treatment and elucidates its underlying molecular mechanisms. Methods A dextran sulfate sodium (DSS)-induced UC mouse model was established, and ASD treatment was administered to observe its effects on colitis and organ toxicity. Inflammation was induced in NCM460 and HT29 cells using lipopolysaccharide (LPS), and ASD treatment was applied to evaluate its anti-inflammatory effects. To assess the involvement of the gut microbiota and metabolite landscape, fecal microbiota transplantation (FMT), 16S rRNA sequencing, and untargeted metabolomics were conducted. Single-cell RNA sequencing (scRNA-seq) was performed using the MGISEQ-2000 platform to characterize the ASD-induced cellular landscape of the colon. Additionally, network pharmacology approaches were employed to predict and validate potential molecular targets of ASD. Results ASD demonstrated significant therapeutic efficacy in UC, as evidenced by attenuated body weight loss, restored colonic length, and improved mucosal barrier integrity. Treatment with ASD substantially remodeled the gut microbiota composition and metabolic profiles, notably elevating the abundance of Akkermansia muciniphila (A. muciniphila) and levels of indole-3-carbinol (I3C). Single-cell resolution analysis revealed that ASD promoted the expansion of Hmgb2+ transit-amplifying cells (TACs) and Muc2+ goblet cells (GCs) in colonic tissues. Mechanistically, we demonstrated that EGFR is a key molecular target of ASD upstream of the MEK/ERK/AP-1 signaling cascade. Conclusion Our study demonstrates that ASD, as a microbiota-modulating therapeutic agent, alleviates intestinal inflammation by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.

ABSTRACT Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa with an increasing global burden and limited therapeutic efficacy. Scutellarein (Scu), a bioactive flavonoid found in various edible plants of Lamiaceae and Verbenaceae, has been shown to possess anti‐inflammatory and antioxidant activities. Herein, we systematically evaluated the effectiveness of scutellarein in the treatment of UC and identified its direct target and underlying inflammation suppression mechanism. Integrated 16S rRNA sequencing and untargeted metabolomics showed that scutellarein preserves gut microbial and metabolic homeostasis and enhances intestinal barrier integrity via enrichment of D‐(‐)‐quinic acid (DQ). Limited proteolysis mass spectrometry (Lip‐MS) identified protein arginine methyltransferase 1 (PRMT1) as a bona fide target of scutellarein. Mechanistic investigations further uncovered that scutellarein directly binds to the Y128 residue of PRMT1, which in turn inhibits STAT3 asymmetric dimethylation and phosphorylation. This cascade collectively downregulates RORγt expression, restrains Th17 differentiation, and ultimately restores the Th17/Treg cell equilibrium. Overall, scutellarein exerts dual protective effects in UC by reinforcing epithelial barrier function through microbiota‐metabolite regulation and suppressing mucosal inflammation via the PRMT1/STAT3/RORγt axis. Our findings not only elucidate a novel multicomponent mechanism for a natural product but also nominate PRMT1 as a compelling new therapeutic target for UC.

Bowel preparation with polyethylene glycol electrolyte solution is indispensable for gastrointestinal endoscopy and related procedures. However, it disrupts gut microbial homeostasis and increases host vulnerability to ensuing infection. In a murine model, we optimized a synbiotic intervention consisting of fructooligosaccharides (FOS) and Clostridium butyricum (C. butyricum) to improve post-cleansing microbiome resilience and mucosal defense. We evaluated its efficacy and longitudinally monitored the dynamics of gut microbiota in response to bowel cleaning and concurrent bacterial challenge infection. Our data show that the bowel preparation induced a persistent microbial perturbation, resulting in an incomplete spontaneous recovery 15 days after the procedure. A 12-day symbiotic intervention significantly enriched alpha diversity and restored the dysbiosis induced by the cleaning. The intervention also increased the Firmicutes/Bacteroidota ratio and the abundance of several key beneficial bacteria in the genera Lactobacillus, Mucispirillum, and Butyricicoccus. Under infectious stress, bowel cleansing markedly aggravated colitis phenotypes, while the intervention alleviated crypt hyperplasia and attenuated inflammatory injury in mice infected with Citrobacter rodentium, resulting in a significant improvement in several colitis indicators. The synbiotic was accompanied by enhanced IL-12/IFN-γ-related antimicrobial responses, increased expression of Muc2 and sIgA, and reshaped bacterial interaction networks disrupted by challenge infection. Our findings demonstrate that the combined administration of FOS and C. butyricum promotes gut microbial homeostasis and host defense. This approach may provide insights into potential dietary strategies for mitigating bowel cleansing-induced microbial disturbances.

N7-methylguanosine (m7G) is one of the most prevalent post-transcriptional modifications of RNA and plays a critical role in RNA translation and stability. As a pivotal m7G regulator, methyltransferase-like 1 (METTL1) is responsible for methyl group transfer during the progression of m7G modification and contributes to the structure and functional regulation of RNA. Accumulating evidence in recent years has revealed that METTL1 plays key roles in various diseases depending on its m7G RNA methyltransferase activity. Elevated levels of METTL1 are typically associated with disease development and adverse consequences. In contrast, METTL1 may act as a disease suppressor in several disorders. While the roles of m7G modifications in disease have been extensively reviewed, the critical functions of METTL1 in various types of disease and the potential targeting of METTL1 for disease treatment have not yet been highlighted. This review describes the various biological functions of METTL1, summarises recent advances in understanding its pathogenic and disease-suppressive functions and discusses the underlying molecular mechanisms. Given that METTL1 can promote or inhibit disease processes, the possibility of applying METTL1 inhibitors and agonists is further discussed, with the goal of providing novel insights for future disease diagnosis and potential intervention targets. KEY POINTS: METTL1-mediated m7G modification is crucial for various biological processes, including RNA stability, maturation and translation. METTL1 has emerged as a critical epigenetic modulator in human illnesses, with its dysregulated expression correlating with multiple diseases progression and presenting opportunities for both diagnostic biomarker development and molecular-targeted therapy. Enormous knowledge gaps persist regarding context-dependent regulatory networks of METTL1 and dynamic m7G modification patterns, necessitating mechanistic interrogation to bridge basic research with clinical translation in precision medicine.

Breast cancer stands as one of the most prevalent malignant tumors threatening women's health and is a leading cause of cancer-related mortality. Its treatment faces significant challenges, including drug tolerance and disease recurrence. Glycolysis serves not only as a critical metabolic pathway for energy acquisition in breast cancer cells but also essentially promotes tumor proliferation, invasion, metastasis, and the development of resistance to therapy. Recent studies have revealed a close association between glycolytic reprogramming and drug resistance in breast cancer, with high-level glycolysis emerging as a hallmark of malignancy, deeply involved in the initiation and progression of tumors. This review summarizes recent advances in research on key enzymes and signaling pathways regulating glycolysis within the bodies of breast cancer patients. It explores in depth these molecular mechanisms and their complex interaction networks, offering a fresh perspective on overcoming drug resistance in breast cancer. Moreover, it underscores the importance of developing specific inhibitors targeting key enzymes and regulators of glycolysis and suggests that combining such inhibitors with existing anticancer drugs could substantially enhance therapeutic outcomes for breast cancer patients and reduce the occurrence of drug resistance.

Tumor immune escape is a pivotal gateway for esophageal squamous cell carcinoma (ESCC) development. Immune checkpoint-blocking therapies, represented by programmed cell death receptor-1/ligand 1 (PD-1/PD-L1) inhibitors, have achieved remarkable breakthroughs in ESCC treatment. However, not all patients with ESCC receive satisfactory clinical benefit. Therefore, identifying novel biomarkers for predicting the efficacy of immunotherapy in ESCC is of great importance. CircNF1 was screened from the circRNAs microarray, and its expression was measured by droplet digital polymerase chain reaction (ddPCR) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in ESCC tissues and serum. Functional experiments were conducted to demonstrate the role of circNF1 in ESCC proliferation, metastasis, and tumor evasion. High-throughput RNA sequencing, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (co-IP), and chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) were performed to clarify the underlying mechanisms of circNF1-mediated tumor progression. The upregulation of circNF1 was closely associated with the response of anti-PD-L1 immunotherapy. Functionally, circNF1 promoted ESCC cell malignant phenotypes and regulated CD8+ T-cell-mediated antitumor immunity. Mechanistically, circNF1 drove the IL-6-induced oncogenic activation of the JAK–STAT3 pathway, which stimulated p-STAT3 binding of the promoter regions of PD-L1. Furthermore, circNF1 physically interacted with annexin A1 (ANXA1), blocking the ANXA1 deubiquitination induced by ubiquitin-specific protease 7 (USP7), resulting in increased interaction between USP7 and PD-L1 and augmented PD-L1 stability. Our findings provide novel insights into the specific regulatory mechanism of PD-L1 in ESCC cells, which offer a new strategy for synergizing with anti-PD-L1 therapy.

N1-methyladenosine (m1A) modification widely occurs in various RNAs, yet its pathophysiological function in tumorigenesis remains poorly understood. Notably, the expression and biological roles of tRNA m1A methyltransferase 6 noncatalytic subunit (TRMT6) in breast cancer, particularly in triple-negative breast cancer (TNBC), are unknown. Herein, it is demonstrated that TRMT6 is markedly elevated in TNBC, due to the H3K4me3 methylation modification occurring at the promoter region to enhance transcription. Through integrated analyses of m1A tRNA methylated RNA immunoprecipitation sequencing, ribosome profiling sequencing, RNA sequencing and data-independent acquisition mass spectrometry, ferritin heavy chain 1 (FTH1) is identified as a downstream target of TRMT6. Mechanistically, it is found that TRMT6 is responsible for the formation of m1A methylation on tRNAs, which increases the translation efficiency of FTH1. Besides, TRMT6 promotes ferritin light chain (FTL) expression at both transcriptional and translational levels, further reinforcing its role in iron metabolism. TRMT6 regulates the malignant progression of TNBC by modulating ferroptosis in tumor cells. Conclusively, the findings indicate that histone methylation-driven TRMT6 is crucial for the translation of FTH1 and FTL, which bridges the understanding of m1A tRNA modification and ferroptosis. These results highlight TRMT6 as a novel potential therapeutic target for TNBC.

BACKGROUND:RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure.METHODS:The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms.RESULTS:The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor.CONCLUSION:Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Neurotransmitter and neuromodulator release by Ca2+-regulated exocytosis is essential for information transmisson between cells. Formation of SNARE complex (soluble N-ethylmaleimide sensitive factor attachment protein receptors) provide energy to bring vesicles and the plasma membranes together and catalyze membrane fusion. The “Ca2+-dependent activator protein for secretion” (CAPS) assumes a pivotal role in facilitating vesicle content release, not only in the nervous system but also in various other secretory tissues. In recent years, great progress has been made in the study of the mechanism of CAPS regulating vesicle secretion. In this review, we summarize recent advances toward the functions and molecular mechanisms of CAPSs in vesicle exocytosis, and contemplate future research directions that will illuminate the molecular mechanisms of neurodegeneration.

N7-methylguanosine (m7G) methylation, one of the most common RNA modifications in eukaryotes, has recently gained considerable attention. The biological functions of m7G modification in RNAs, including tRNA, rRNA, mRNA, and miRNA, remain largely unknown in human diseases. Owing to rapid advances in high-throughput technologies, increasing evidence suggests that m7G modification plays a critical role in cancer initiation and progression. As m7G modification and hallmarks of cancer are inextricably linked together, targeting m7G regulators may provide new possibilities for future cancer diagnoses and potential intervention targets. This review summarizes various detection methods for m7G modification, recent advances in m7G modification and tumor biology regarding their interplay and regulatory mechanisms. We conclude with an outlook on the future of diagnosing and treating m7G-related diseases.

Aerobic glycolysis has been considered as a hallmark of colorectal cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients' lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via β-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/β-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/β-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.

Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated RAS protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/AKT pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and RAS interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis.

Mounting evidence suggests that long non-coding RNAs play a critical role in the occurrence and development of human malignancies. Nonetheless, it remains unknown whether Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1 (BBOX1-AS1) participates in the regulation of esophageal squamous cell carcinoma (ESCC) carcinogenesis. Herein, we validated that BBOX1-AS1 was notably overexpressed in ESCC tissues compared to the adjacent non-tumor tissues and significantly correlated with tumor sizes. BBOX1-AS1 enhanced the malignant behavior of ESCC cells in vitro, such as cell proliferation, migration, and invasion. In addition, knockdown of BBOX1-AS1 augmented the proportion of apoptotic cells in ESCC cells. Mechanistically, BBOX1-AS1 regulated HOXB7 expression, and rescue experiments indicated that silencing of HOXB7 could abolish the malignant phenotypes mediated by BBOX1-AS1 to a certain extent. Moreover, HOXB7 participated in the activation of the Wnt/β-catenin signaling pathway. In summary, our findings substantiated that BBOX1-AS1 could activate the Wnt/β-catenin pathway by upregulating HOXB7 expression to promote ESCC progression, providing a rationale to develop novel therapeutic approaches.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive gastrointestinal cancers with high incidence and mortality. Therefore, it is necessary to identify novel sensitive and specific biomarkers for ESCC detection and treatment. Circular RNAs (circRNAs) are a type of noncoding RNAs featured by their covalently closed circular structure. This special structure makes circRNAs more stable in mammalian cells, coupled with their great abundance and tissue specificity, suggesting circRNAs may present enormous potential to be explored as valuable prognostic and diagnostic biomarkers for tumor. Mounting studies verified the critical roles of circRNAs in regulating ESCC cells malignant behaviors. Here, we summarized the current progresses in a handful of aberrantly expressed circRNAs, and elucidated their biological function and clinical significance in ESCC, and introduced a series of databases for circRNA research. With the improved advancement in high-throughput sequencing and bioinformatics technique, new frontiers of circRNAs will pave the path for the development of precision treatment in ESCC.

Accumulating evidence has revealed that m6A modification, the predominant RNA modification in eukaryotes, adds a novel layer of regulation to the gene expression. Dynamic and reversible m6A modification implements sophisticated and crucial functions in RNA metabolism, including generation, splicing, stability, and translation in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). Furthermore, m6A modification plays a determining role in producing various m6A-labeling RNA outcomes, thereby affecting several functional processes, including tumorigenesis and progression. Herein, we highlighted current advances in m6A modification and the regulatory mechanisms underlying mRNAs and ncRNAs in distinct cancer stages. Meanwhile, we also focused on the therapeutic significance of m6A regulators in clinical cancer treatment.

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive. The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation. IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients.

Recently, ample evidence indicated that numerous aberrantly expressed long non-coding RNAs (lncRNAs) participated in the development of multiple malignancies. However, the expression and function of lncRNA LOXL1-AS1 in mediating esophageal squamous cell carcinoma (ESCC) carcinogenesis remains largely elusive. Here we validated that LOXL1-AS1 was significantly upregulated in ESCC tissues compared with the corresponding adjacent non-neoplastic tissues, and LOXL1-AS1 expression was positively correlated with ESCC patients' lymph node metastasis. Besides, LOXL1-AS1 knockdown impaired ESCC cells proliferation, migration and invasion capabilities in vitro. Furthermore, inhibiting LOXL1-AS1 in ESCC cells increased the percentage of cells at the G1 phase, accompanied by reducing in S phase in contrast to scramble control, and silencing of LOXL1-AS1 evoked ESCC cell apoptosis. From high throughput RNA sequencing (RNA-seq) analysis, we identified that differentially expressed in squamous cell carcinoma 1 (DESC1) was a critical downstream target of LOXL1-AS1. Taken together, we demonstrated the function and mechanism of LOXL1-AS1 in contributing ESCC progression for the first time, and indicated LOXL1-AS1 may be a novel therapeutic biomarker of ESCC.

Background Ovarian cancer is one of the most common gynecological tumors, and among gynecological tumors, its incidence and mortality rates are fairly high. However, the pathogenesis of ovarian cancer is not clear. The present study aimed to investigate the differentially expressed genes and signaling pathways associated with ovarian cancer by bioinformatics analysis. Methods The data from three mRNA expression profiling microarrays (GSE14407, GSE29450, and GSE54388) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes between ovarian cancer tissues and normal tissues were identified using R software. The overlapping genes from the three GEO datasets were identified, and profound analysis was performed. The overlapping genes were used for pathway and Gene Ontology (GO) functional enrichment analysis using the Metascape online tool. Protein-protein interactions were analyzed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Subnetwork models were selected using the plugin molecular complex detection (MCODE) application in Cytoscape. Kaplan-Meier curves were used to analyze the univariate survival outcomes of the hub genes. The Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to validate hub genes. Results In total, 708 overlapping genes were identified through analyses of the three microarray datasets (GSE14407, GSE29450, and GSE54388). These genes mainly participated in mitotic sister chromatid segregation, regulation of chromosome segregation and regulation of the cell cycle process. High CCNA2 expression was associated with poor overall survival (OS) and tumor stage. The expression of CDK1, CDC20, CCNB1, BUB1B, CCNA2, KIF11, CDCA8, KIF2C, NDC80 and TOP2A was increased in ovarian cancer tissues compared with normal tissues according to the Oncomine database. Higher expression levels of these seven candidate genes in ovarian cancer tissues compared with normal tissues were observed by GEPIA. The protein expression levels of CCNA2, CCNB1, CDC20, CDCA8, CDK1, KIF11 and TOP2A were high in ovarian cancer tissues, which was further confirmed via the HPA database. Conclusion Taken together, our study provided evidence concerning the altered expression of genes in ovarian cancer tissues compared with normal tissues. In vivo and in vitro experiments are required to verify the results of the present study.

Regenerating islet-derived protein 1-alpha (REG1A) was abnormally upregulated in a series of gastrointestinal inflammatory disorders. However, the potential biological function and underlying regulatory mechanisms of the increased REG1A in inflammatory bowel disease (IBD) pathogenesis remain to be fully elucidated. In this study, we uncovered that REG1A was substantially increased in the inflamed colorectal tissues of IBD patients. And the aberrantly expressed REG1A in intestinal epithelial cells (IEC) prominently inhibited inflammatory responses, promoted cell proliferation and suppressed epithelial apoptosis. Mechanically, IL-6 and IL-22 markedly activated REG1A transcription through triggering JAK/STAT3 signaling pathway. In addition, overexpression of REG1A in mice by systematic delivery of REG1A lentivirus remarkably alleviated DSS-induced inflammatory injury and maintained the integrity of intestinal mucosal barrier. Taken together, our data demonstrated that the novel proliferative factor REG1A controlled by IL-6/IL-22-JAK-STAT3 signaling may provide a promising therapeutic target for patients with IBD.

Background: Annexin A1 (ANXA1) was discovered to show various effects during tumor initiation and development in a tumor-specific manner.However, the function of ANXA1 in papillary thyroid carcinoma (PTC) has not been reported.Methods: Bioinformatic analyses, RT-PCR and immunohistochemistry were employed to determine the ANXA1 expression level in PTC.Both gain-and loss-of-function studies, including CCK-8, EdU assay, transwell experiment and wound-healing assay were used to investigate the role of ANXA1 in PTC progression.GSEA enrichment analysis was utilized to explore the potential mechanisms of ANXA1 mediated downstream signaling, and ELISA, RT-PCR and western blot were used to confirm the relevance.Results: ANXA1 expression was prominently upregulated in PTC tumor tissues.Ectopic expression of ANXA1 expedited PTC cell proliferation, migration and invasion, whereas ANXA1 knockdown exhibited the opposing trends.Mechanistic investigations showed that ANXA1 regulated epithelial-mesenchymal transition (EMT) and activated the IL-6/JAK2/STAT3 pathway to contribute to PTC malignant behaviors.In particular, loss of ANXA1 retarded tumor burden and suppressed lung metastasis in vivo.Conclusions: In conclusion, our findings identified ANXA1 as a pivotal oncogene during PTC carcinogenesis and ANXA1 might function as a promising therapeutic target and prognostic marker for PTC.