Sepsis as a Potential Risk Factor for Upper Gastrointestinal Bleeding in Critically Ill Patients: A Systematic Review and Meta-analysis.

Purpose: Sepsis is a common and critical condition in intensive care units (ICUs) known to complicate patient outcomes. Previous studies have indicated an association between sepsis and various ICU morbidities, including upper gastrointestinal bleeding (UGIB). However, the extent of this relationship and its implications in ICU settings remain inadequately quantified. This study aims to elucidate the association between sepsis and the risk of UGIB in ICU patients. Methods: A comprehensive meta-analysis was conducted, encompassing nine studies with a total of nearly 9000 participants. These studies reported events for both sepsis and nonsepsis patients separately. Pooled odds ratios (ORs) were calculated to assess the risk of UGIB in septic versus nonseptic ICU patients. Subgroup analyses were conducted based on age and study design, and both unadjusted and adjusted ORs were examined. Results: The pooled OR indicated a significant association between sepsis and UGIB (OR = 3.276, 95% CI: 1.931 to 5.557). Moderate heterogeneity was observed (I² = 43.9%). The association was significant in adults (pooled OR = 4.083) but not in children. No difference in association was found based on the study design. Unadjusted and adjusted ORs differed slightly, indicating the influence of confounding factors. Conclusion: This meta-analysis reveals a significant association between sepsis and an increased risk of UGIB in ICU patients, particularly in adults. These findings highlight the need for vigilant monitoring and proactive management of septic ICU patients to mitigate the risk of UGIB. Future research should focus on understanding the underlying mechanisms and developing tailored preventive strategies.

The Anti-Breast Cancer Activity of Dihydroartemisinin-5-methylisatin Hybrids Tethered via Different Carbon Spacers.

Sixteen dihydroartemisinin-5-methylisatin hybrids 6a-c and 7a-m tethered via different carbon spacers were assessed for their antiproliferative activity against MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines as well as cytotoxicity towards MCF-10A cells to investigate the influence of the length of carbon spacers on the activity. The preliminary results illustrated that the length of the carbon spacer was the main parameter which affected the activity, and hybrids tethered via the two-carbon linker showed the highest activity. Amongst the synthesized hybrids, the representative hybrid 7a (IC50: 15.3-20.1 µM) not only demonstrated profound activity against both drug-sensitive and drug-resistant breast cancer cell lines, but also possessed excellent safety and selectivity profile. Collectivity, hybrid 7a was a promising candidate for the treatment of both drug-sensitive and drug-resistant breast cancers and worthy of further preclinical evaluations.

The Value of Pulmonary Bedside Ultrasound System in the Evaluation of Severity and Prognosis of Acute Lung Injury.

OBJECTIVE: To evaluate the value of pulmonary bedside ultrasound system in the assessment of severity and prognosis of acute lung injury (ALI). METHOD: Seventy-two ALI patients in the intensive care unit (ICU) of our hospital from April 2019 to April 2021 were selected as subjects. The changes of lung ultrasound score (LUS) and parameters at D1, D2, and D3 after admission were analyzed (LUS, oxygenation index (PaO2/FiO2), Acute Physiology and Chronic Health Evaluation II (APACHE-II), and Sequential Organ Failure Assessment (SOFA) score). Pearson correlation analysis was used to assess the relationship between LUS and PaO2/FiO2, APACHE-II score, and SOFA score at D1, D2, and D3. Logistic regression analysis was used for influencing factors for the prognosis of ALI patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of baseline LUS, PaO2/FiO2, APACHE-II score, and SOFA score for the prognosis of ALI patients. RESULT: LUSs at D1, D2 and D3 showed an increasing trend with the increase of disease severity (P < 0.05). From D1 to D3, LUS, PaO2/FiO2, APACHE-II score, and SOFA score showed a downward trend (P < 0.05). LUS was negatively correlated with PaO2/FiO2 at D1, D2, and D3 but positively correlated with APACHE-II score and SOFA score (P < 0.05). Logistic regression analysis showed that after controlling for age, PaO2 and PaCO2, an increase in baseline LUS, APACHE-II score, SOFA score, and a decrease in PaO2/FiO2 were independent risk factors for death at 28 d in ALI patients (P < 0.05). ROC curve showed that LUS, PaO2/FiO2, APACHE-II score, and SOFA score were combined to predict the prognosis of ALI patients with the highest AUC value of 0.920, corresponding sensitivity of 88.89%, and specificity of 95.56%. CONCLUSION: LUS can evaluate the change of pulmonary ventilation area in ALI patients, further evaluate the severity of the disease, and effectively predict the prognosis of patients.

miR-150 and SRPK1 regulate AKT3 expression to participate in LPS-induced inflammatory response.

miR-150 was found to target the 3'-untranslated regions of AKT3, and the AKT pathway was affected by SR protein kinase 1 (SRPK1). However, the expression and significance of miR-150, AKT3 and SRPK1 in acute lung injury (ALI) were not clear. Here, we found that the expression of miR-150 was significantly reduced, while the expression of AKT3 and SRPK1 were markedly increased in LPS-treated A549, THP-1 and RAW 264.7 cells. miR-150 significantly decreased levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α, reduced the expression of AKT3, but had no impact on SRPK1 expression compared with the control group in LPS-treated A549, THP-1 and RAW 264.7 cells. AKT3 silencing only reduced the production of pro-inflammatory cytokines and showed no effect on miR-150 and SRPK1 expression. Finally, we observed that miR-150 mimics and/or silencing of SRPK1 decreased the expression of AKT3 mRNA. Besides, over-expression of miR-150 or silencing of SRPK1 also reduced the expression of AKT3 protein, which exhibited the lowest level in the miR-150 mimics plus si-SRPK1 group. However, si-SRPK1 had no effect on miR-150 level. In conclusion, miR-150 and SRPK1 separately and cooperatively participate into inflammatory responses in ALI through regulating AKT3 pathway. Increased miR-150 and silenced SRPK1 may be a novel potential factor for preventing and treating more inflammatory lung diseases.

MiR-30a-5p ameliorates LPS-induced inflammatory injury in human A549 cells and mice via targeting RUNX2.

In this study, we aim to investigate the role of miR-30a-5p in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) using LPS-induced A549 cells and mice. We found cell viability was significantly declined accompanied by cell apoptosis and cell cycle arrest at G0/G1 phase in LPS-treated A549 cells. MiR-30a-5p was down-regulated by LPS treatment and miR-30a-5p significantly protected A549 cells from LPS-induced injury by increasing cell viability, reducing cell apoptosis, promoting cell cycle progression, and inhibiting inflammatory reactions. Dual-luciferase activity demonstrated that RUNX2 was a direct target for miR-30a-5p and its expression was negatively and directly regulated by miR-30a-5p. Over-expression of RUNX2 weakened the inhibitory effect of miR-30a-5p on inflammatory injury. In vivo, over-expression of miR-30a-5p alleviated LPS-induced inflammatory responses and lung injury in LPS-administrated mice. Besides, miR-30a-5p repressed LPS-elevated phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK), IκBα degradation, and NF-κB p65 phosphorylation. In conclusion, miR-30a-5p ameliorates LPS-induced inflammatory injury in A549 cells and mice via targeting RUNX2 and related signaling pathways, thereby influencing the progression of ARDS.

Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression.

The aberrant expression of microRNAs (miRNAs) is associated with the pathogenesis of inflammation-related diseases. However, the biological functions of miR-21 in acute lung injury (ALI) remain largely unknown. In this study, the level of miR-21 was obviously increased, but B cell lymphoma-2 (Bcl-2) expression was markedly decreased in LPS-treated human pulmonary alveolar epithelial cells (HPAEpiC). Suppression of miR-21 attenuated LPS-induced apoptosis and inflammation in HPAEpiC and promoted the survival of mice with ALI by decreasing the inflammatory cell count, release of cytokines and permeability in lung tissues. Importantly, Bcl-2 was a direct target of miR-21, and its expression was significantly inhibited by miR-21 mimics at a post-transcriptional level. Besides, Bcl-2 over-expression reversed miR-21-induced apoptosis and inflammation status and showed synergic effects with miR-21 inhibitor in LPS-treated HPAEpiC. In conclusion, inhibition of miR-21 could ameliorate apoptosis and inflammation by restoring the expression of Bcl-2 in LPS-induced HPAEpiC and mice, which might provide therapeutic strategies for the treatment of ALI.

MiR-297 alleviates LPS-induced A549 cell and mice lung injury via targeting cyclin dependent kinase 8.

In recent decades, microRNAs (miRNAs) have been reported to play an important role in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To explore the underlying mechanisms of miR-297 in ALI/ARDS, we investigated its role in lipopolysaccharide (LPS)-induced A549 cell and mice lung injury model. We found that the expression of miR-297 decreased in LPS-induced A549 cells or serum of ALI/ARDS mice. Moreover, LPS suppressed A549 cell viability, promoted apoptosis and increased the expressions of inflammatory and autophagy-related factors. Conversely, overexpression of miR-297 increased cell proliferation and reduced cell apoptosis, and alleviated inflammatory cytokines secretion and autophagy in the presence of LPS. Importantly, miR-297 directly inhibited transcription of cyclin dependent kinase 8 (CDK8) by binding to the 3'-untranslated region (3'-UTR) of CDK8 mRNA, and the expression of CDK8 was negatively regulated by miR-297. Silencing of CDK8 promoted the anti-inflammatory and anti-apoptotic effects of miR-297 in LPS-mediated A549 cells. The expressions of phosphorylated p65 (p-p65)/p65 and phosphorylated inhibitor kappa B-α (p-IκBα)/IκBα were dramatically decreased by miR-297 mimics and silencing of CDK8. In vivo, miR-297 alleviated LPS-induced inflammatory responses and lung injury in ALI/ARDS mice. In conclusion, our findings suggested that miR-297 affects nuclear factor-kappa B (NF-κB) pathway to alleviate LPS-induced A549 cell and mice lung injury via targeting CDK8 expression.

MiR-150 attenuates LPS-induced acute lung injury via targeting AKT3.

Acute lung injury (ALI) and its severe manifestation of acute respiratory distress syndrome (ARDS) in human lung are induced by inflammatory cytokines and endogenous factors such as miRNAs. However, the role of miR-150 in lipopolysaccharide (LPS)-induced ALI is not clear. Here, we found miR-150 expression was significantly reduced in the serum of patients with ARDS, and negatively associated with the disease severity and 28-day survival of ARDS. In vivo, miR-150 decreased total cell and neutrophil counts, and production of inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) as well as levels of total protein, albumin and IgM in the bronchoalveolar lavage (BAL) fluid in LPS-induced ALI mice. Meanwhile, miR-150 improved the 72 h survival rate of LPS-induced ALI mice. In-vitro assays demonstrated that miR-150 alleviated LPS-induced A549 cell apoptosis, autophagy, and release of inflammatory cytokines. Further, AKT3 was a direct target of miR-150. Silencing of AKT3 partially reversed LPS-induced A549 cell injury, and enhanced the protective effects of miR-150. In addition, miR-150 or si-AKT3 effectively inhibited the phosphorylation levels of c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) (p65 and IκBα). In conclusion, miR-150 alleviated LPS-induced acute lung injury via directly targeting AKT3 expression or regulating JNK and NF-κB pathways, which may be a promising therapeutic strategy to treat ALI/ARDS.

MiR-216b suppresses cell proliferation, migration, invasion, and epithelial-mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer.

Background/aims: MiR-216b and forkhead box M1 (FOXM1) were demonstrated to exert their biological effects on the development and progression of tumors. This study aimed to investigate the expression and role of miR-216b and FOXM1 in tissues and cell lines of non-small cell lung cancer (NSCLC). Methods: The expressions of miR-216b and FOXM1 in NSCLC tissues and cells were detected by qRT-PCR and Western blot analysis. Cell proliferation was measured by CCK-8 assay. Cell migration and invasion were confirmed by Transwell assay. Finally, the bioinformatics and dual-luciferase reporter assay were conducted to validate the relationship of miR-216b and FOXM1. Results: Compared with normal tissues and cells, the expression of miR-216b was obviously decreased in NSCLC tissues and cells. However, the expressions of FOXM1 mRNA and protein were significantly increased, and negatively correlated with the expression of miR-216b. Multivariate Cox's regression analysis suggested that miR-216b or FOXM1 expression was an independent prognostic factor for patients with NSCLC. MiR-216b overexpression remarkably repressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. The bioinformatics and dual-luciferase reporter assay validated that the 3'-untranslated region (3'-UTR) of FOXM1 mRNA was indeed a direct target of FOXM1. In vitro, overexpression of FOXM1 partially eliminated inhibitory effects of miR-216b on cell proliferation, migration, and invasion, whereas inhibition of FOXM1 contributed to inhibitory effects mediated by miR-216b. Conclusion: MiR-216b inhibits cell proliferation, migration, invasion, and EMT by targeting the expression of FOXM1 in human NSCLC. These findings suggested a potential therapeutic role of miR-216b in patients of NSCLC.

miR-297 Protects Human Umbilical Vein Endothelial Cells against LPS-Induced Inflammatory Response and Apoptosis.

BACKGROUND/AIMS: Recently, microRNA-297 (miR-297) and signal transducer and activator of transcription 3 (STAT3) have been demonstrated to be involved in dysfunction of vascular endothelial cells and inflammatory conditions, such as sepsis. The present study aimed to investigate the role of miR-297 and STAT3 in lipopolysaccharide (LPS)-induced inflammatory human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were stimulated by different concentrations of LPS. miR-297 mimics were transfected into HUVECs to overexpress miR-297. The qRT-PCR was used to measure the expression level of miR-297. Western blot was used to detect the expressions of STAT3, inflammatory cytokines, adhesion molecules and apoptosis-related proteins. Cell apoptosis was determined by flow cytometry. RESULTS: Compared with parental HUVECs, the expression of miR-297 was significantly down-regulated, while the expression of STAT3 was obviously up-regulated in LPS-induced HUVECs. The expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were also increased in LPS-induced HUVECs than those in parental HUVECs. In addition, LPS induced apoptosis of HUVECs through up-regulation of Bax and cleaved caspase 3 expressions. Conversely, miR-297 mimics inhibited LPS-activated expressions of STAT3, inflammatory cytokines, and adhesion molecules, and protected HUVECs against LPS-induced apoptosis through inhibition of Bax and cleaved caspase 3 expressions. Mechanistically, the 3'-untranslated region (3'-UTR) of STAT3 mRNA was validated as a direct target of miR-297. Over-expression of STAT3 partially abrogated protective effects of miR-297, whereas silencin g of STAT3 contributed to miR-297-mediated biological effects. CONCLUSION: miR-297 protects HUVECs against LPS-induced inflammatory response and apoptosis by targeting STAT3 pathway. Thus, miR-297 may be a promising therapeutic target for patients with sepsis.

PDE5 inhibitor protects the mitochondrial function of hypoxic myocardial cells.

Protective effect of phosphodiesterase 5 (PDE5) inhibitor sildenafil on hypoxic injury of isolated myocardial cells and its mechanism of action were investigated. Myocardial cells of neonatal mice were isolated, cultured and divided into blank, control, and PDE5 inhibitor group. Cells in the control and the PDE5 inhibitor group were treated with hypoxia and serum deprivation for 6 h to simulate the myocardial ischemia process in vivo, while those in the PDE5 inhibitor group were treated with 1 µmol/l sildenafil. The cell viability was detected via Cell Counting kit-8 (CCK-8), the cytotoxicity was detected via lactate dehydrogenase release assay, and the apoptosis level was detected via flow cytometry, Hoechst staining and caspase-3 activity assay. Moreover, changes in mitochondrial membrane potential of myocardial cells were detected via JC-1 staining and flow cytometry, fluorescein adenosine triphosphate (ATP) assay kit was used to detect the production of ATP in myocardial cells, and reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the level of Sirt3 messenger ribonucleic acid (mRNA) in myocardial cells. Finally, the expression and changes of Sirt3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and acetylated PGC-1α were detected via western blot analysis. After hypoxia treatment, the cell viability was decreased, the cytotoxic effect was enhanced, the percentage of apoptosis was increased, the activity of apoptosis-related protein was increased, the mitochondrial membrane potential was decreased, the production of ATP was reduced, the expression of Sirt3 was decreased, and the acetylation level of PGC-1α was increased. However, after pretreatment with sildenafil, the damage to membrane potential of myocardial cells was significantly alleviated, and the production of ATP was increased. At the same time, myocardial cell apoptosis was decreased, Sirt3 expression was increased and PGC-1α acetylation was decreased. PDE5 inhibitor inhibits apoptosis of hypoxic myocardial cells through protecting mitochondrial function.

MiR-216b suppresses colorectal cancer proliferation, migration, and invasion by targeting SRPK1.

BACKGROUND: MiR-216b has been reported to be involved in the development of some cancers, however, the role of miR-216b in colorectal cancer (CRC) remains unclear. PURPOSE: This study aimed to investigate the mechanism underlying miR-216b-induced CRC development. METHODS: We detected the expression of miR-216b in 80 cases of CRC tissues and cell lines, and further analyzed the association between miR-216b and clinical pathological indicators as well as prognosis. In vitro, the miR-216b overexpression cell model was established for further functional assay. RESULTS: We demonstrated that miR-216b in CRC tissues and cell lines was markedly decreased compared with corresponding adjacent normal tissues and colonic mucosal epithelial cell line, and was obviously associated with the TNM stage, lymph node metastases, and poor overall survival as well as recurrence-free survival. Furthermore, we found that miR-216b inhibited cell proliferation, cell cycle, migration, and invasion by targeting 3'-UTR of SRPK1. Besides, SRPK1 over-expression reversed miR-216b-inhibited cell proliferation, migration and invasion, while SRPK1 inhibition aggravated these effects. CONCLUSIONS: We identified that miR-216b suppresses colorectal cancer proliferation, migration and invasion by targeting SRPK1, which shed light on how miR-216b functions in CRC pathogenesis.

MiR-150 predicts survival in patients with sepsis and inhibits LPS-induced inflammatory factors and apoptosis by targeting NF-κB1 in human umbilical vein endothelial cells.

MiR-150 is involved into some pathological processes, such as tumorigenesis and autoimmune diseases. However, little is known about the involvement of miR-150 in human sepsis. In this study, plasma miR-150 level had a diagnostic and independent prognostic value in patients with sepsis, and negatively correlated with renal dysfunction and 28-day survival as well as plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). MiR-150 expression was also significantly decreased in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice with sepsis after lipopolysaccharides (LPS) treatment. In-vitro, miR-150 over-expression protected HUVECs from LPS-induced apoptosis and the expressions of nuclear factor-κB1 (NF-κB1), IL-6, TNF-α, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Furthermore, NF-κB1 was identified as a direct target of miR-150. Restored NF-κB1 expression antagonized the protective effects of miR-150, while suppression of NF-κB1 enhanced these protective effects. Our findings indicate miR-150 predicts survival in patients with sepsis and inhibits LPS-induced inflammatory factors and apoptosis by targeting NF-κB1 in human umbilical vein endothelial cells. Thus, miR-150 may be a useful biomarker or target in the diagnosis, prognosis and treatment of patients with sepsis.

Proteinase-activated receptor 2 promotes tumor cell proliferation and metastasis by inducing epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma.

AIM: To clarify the role of proteinase-activated receptor 2 (PAR2) in hepatocellular carcinoma, especially in the process of metastasis. METHODS: PAR2 expression levels were assessed by qRT-PCR and immunohistochemistry (IHC) in patient tissues and in hepatocellular carcinoma cell lines SMMC-7721 and HepG2. Cell proliferation and metastasis were assessed both in vitro and in vitro. Immunoblotting was carried out to monitor the levels of mitogen-activated protein kinase (MAPK) and epithelial-mesenchymal transition markers. RESULTS: The prognosis was significantly poorer in patients with high PAR2 levels than in those with low PAR2 levels. Patients with high PAR2 levels had advanced tumor stage (P = 0.001, chi-square test), larger tumor size (P = 0.032, chi-square test), and high microvascular invasion rate (P = 0.037, chi-square test). The proliferation and metastasis ability of SMMC-7721 and HepG2 cells was increased after PAR2 overexpression, while knockdown of PAR2 decreased the proliferation and metastasis ability of SMMC-7721 and HepG2 cells. Knockdown of PAR2 also inhibited hepatocellular carcinoma tumor cell growth and liver metastasis in nude mice. Mechanistically, PAR2 increased the proliferation ability of SMMC-7721 and HepG2 cells via ERK activation. Activated ERK further promoted the epithelial-mesenchymal transition of these cells, which endowed them with enhanced migration and invasion ability. CONCLUSION: These data suggest that PAR2 plays an important role in the proliferation and metastasis of hepatocellular carcinoma. Therefore, targeting PAR2 may present a favorable target for treatment of this malignancy.

miR-136 Inhibits Malignant Progression of Hepatocellular Carcinoma Cells by Targeting Cyclooxygenase 2.

MicroRNAs (miRNAs) play a vital role in regulating tumor progression. Dysregulated miR-136 expression was linked to the development of various human cancers. In the present study, we investigated the expression and relationship of miR-136 and COX2 in hepatocellular carcinoma (HCC) using relevant experiments, involving CCK-8, Transwell assay, and luciferase reporter assay. We demonstrated that miR-136 expression is obviously decreased in HCC tissues and cells, and negatively correlated with the expression of COX2 mRNA. In vitro assay revealed that overexpression of miR-136 significantly changed the expression of proliferation- and metastasis-related proteins and inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Dual-luciferase reporter assay validated that the 3'-untranslated region (3'-UTR) of COX2 is a direct target of miR-136. Furthermore, COX2 siRNA partially enhanced the miR-136 overexpression-induced inhibitory effects. In conclusion, miR-136 was vital in the regulation of HCC cell proliferation and metastasis by targeting COX2. Thus, our findings provided novel evidence that miR-136 might be recommended as a potential target for the diagnosis and treatment of HCC patients.

The crucial role of SRPK1 in IGF-1-induced EMT of human gastric cancer.

In recent years, the insulin-like growth factor (IGF-1) and serine-arginine protein kinase 1 (SRPK1) have been reported to be implicated in the pithelial-mesenchymal transition (EMT) in many kinds of malignancies. However, the potential roles of IGF-1-SRPK1 signaling in the EMT of gastric cancer (GC) have not been investigated. In the present study, the in-vitro assays were used to investigate the molecular role of SRPK1 in cell cycle, motility and invasiveness. We demonstrated that the expressions of SRPK1 or insulin-like growth factor receptor 1 (IGF1R) were significantly increased in GC tissues and cells than those in normal tissues and GES-1 cells, and closely associated with metastasis, stage and prognosis. Western blot analysis showed that IGF-1 treatment can induce the expression of p-AKT and EMT biomarkers (N-cadherin, MMP2 and Slug) in a dose-dependent fashion in MGC803 and BGC823 cells. On the other hand, the knockdown of SRPK1 attenuated IGF-1-induced increase of EMT biomarkers and p-AKT. Besides, in-vitro analysis showed that knockdown of SRPK1 induced cell cycle arrest in G0/G1 phase, and affected cell migration and invasion. In conclusion, IGF-1-IGF1R pathway induced the expression of SRPK1 to control the progression of EMT via AKT pathway in the development of GC. Our findings lay a promising foundation for the IGF-1-IGF1R axis-targeting therapy in GC patients.