H19 encourages aerobic glycolysis and cell growth in gastric cancer cells through the axis of microRNA-19a-3p and phosphoglycerate kinase 1.

Numerous studies have been conducted on long non-coding RNAs (lncRNAs) in human tumors like gastric cancer (GC). Our research uncovers how aerobic glycolysis and cell proliferation in gastric cancer cells are related to H19. We discovered that H19 was highly expressed in tumor tissues and that patients with higher H19 expression have a poorer prognosis. Intriguingly, we applied the subcellular isolation, luciferase reporter, western blot analysis, MTT, colony formation experiments, and CDX Model in Mice to verify that H19 regulates aerobic glycolysis towards GC cell growth by H19/microRNA (miR)-19a-3p/phosphoglycerate kinase 1 (PGK1) axis. Together, our research offers proof that the H19/miR-19a-3p/PGK1 pathway aids in the regulation of aerobic glycolysis and cell proliferation in GC. This may offer an opportunity for novel therapeutic approaches to the treatment of GC.

Long non-coding RNAs and pancreatic cancer: A multifaceted view.

Pancreatic cancer (PC) is a highly malignant disease with a 5-year survival rate of only 10%. Families with PC are at greater risk, as are type 2 diabetes, pancreatitis, and other factors. Insufficient early detection methods make this cancer have a poor prognosis. Additionally, the molecular mechanisms underlying PC development remain unclear. Increasing evidence suggests that long non-coding RNAs (lncRNAs) contribute to PC pathology,which may control gene expression by recruiting histone modification complexes to chromatin and interacting with proteins and RNAs. In recent studies, abnormal regulation of lncRNAs has been implicated in PC proliferation, metastasis, invasion, angiogenesis, apoptosis, and chemotherapy resistance suggesting potential clinical implications. The paper reviews the progress of lncRNA research in PC about diabetes mellitus, pancreatitis, cancer metastasis, tumor microenvironment regulation, and chemoresistance. Furthermore, lncRNAs may serve as potential therapeutic targets and biomarkers for PC diagnosis and prognosis. This will help improve PC patients' survival rate from a lncRNA perspective.

Bioinformatic and experimental analyses of key biomarkers in pancreatic cancer.

The present study aimed to screen the key genes in pancreatic cancer and to explore the pathogenesis of pancreatic cancer. A total of three expression profiling datasets (GSE28735, GSE16515 and GSE15471) associated with pancreatic cancer were retrieved from the public gene chip database. The differentially expressed genes (DEGs) were screened by GEO2R and subjected to Gene Ontology (GO) and signaling pathway enrichment analysis. Furthermore, a protein interaction network was constructed. The GEPIA online database was used to screen for genes that affect the prognosis of pancreatic cancer. Finally, cell functional experiments were performed on the selected key genes. A total of 72 DEGs were identified, including 52 upregulated and 20 downregulated genes. Enrichment analysis revealed roles of the DEGs in endodermal cell differentiation, cell adhesion, extracellular matrix-receptor interaction and PI3K-Akt signaling pathway. In total, 10 key nodal genes were identified, including integrin subunit α 2 (ITGA2), ITGB6 and collagen α 1 chain 1. Through survival analysis, two genes with an impact on the prognosis of pancreatic cancer were identified, namely ITGA2 and ITGB6. Silencing of ITGB6 in a pancreatic cancer cell line significantly suppressed cell proliferation and induced cell cycle arrest at G2/M phase. The identified key genes and signaling pathways may help to deepen the understanding of the molecular mechanisms involved in pancreatic cancer and provide a theoretical basis to develop novel therapies.

Identification of G-protein signaling modulator 2 as a diagnostic and prognostic biomarker of pancreatic adenocarcinoma: an exploration of its regulatory mechanisms.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) has a high rate of mortality. Unfortunately, it is difficult to diagnosis. This study aimed to develop a more in-depth understanding of the disease. METHODS: A total of 177 patients with PAAD were recruited from The Cancer Genome Atlas (TCGA) database. Microarray analysis was performed to identify differentially expressed genes (DEGs) in PAAD. The microarray data were adapted to the ingenuity pathway analysis (IPA) for annotation and visualization, followed by protein-protein interaction (PPI) network analysis. In vitro transwell migration assays were conducted to explore the molecular and functional characteristics of pancreatic adenocarcinoma cells (PANC-1) with stable low expression of G-protein signaling modulator 2 (GPSM2). Expression of GPSM2 and the associated hub genes were detected by reverse transcription-quantitative polymerase chain reaction (qPCR). RESULTS: The overexpression of GPSM2 was proved in PAAD, as compared with the healthy tissues, as well as its correlation with history of chronic pancreatitis, T stage, TNM stage and tumor grade. We described it as an independent prognostic factor and found that it could influence the infiltration of immune cells in the tumor microenvironment. Silencing of GPSM2 restrained the and migration of the cells. Microarray analysis identified 1,631 DEGs in PAAD cells. The PPI network analysis identified hub genes including CD44, ITGB1, ITGB5, ITGA2, ITGA5, AKT1, EGFR, NRAS and MAP2K1, and their relationship with GPSM2 was confirmed by qPCR. CONCLUSIONS: GPSM2 is a novel prognostic factor and therapeutic target for PAAD. GPSM2 promoted the migration of pancreatic adenocarcinoma cells .Targeting GPSM2 and its downstream genes may prolong the survival time of patients with PAAD.

Expression profile of lncRNAs and mRNAs in intestinal macrophages.

Non-coding RNAs (ncRNAs) have been previously reported to serve an important role in transcription. In addition, several studies have revealed that long ncRNAs (lncRNAs) have a crucial role in human diseases. However, the association between lncRNAs and inflammation­induced intestinal macrophages in the intestinal mucosal barrier has remained elusive. In the present study, intestinal macrophages from healthy Sprague Dawley rats were divided into two groups: The experimental group, consisting of intestinal macrophages treated with 1 mg/l lipopolysaccharide (LPS) and the control group, composed of untreated cells. Differentially expressed (DE) lncRNAs and mRNAs between the control and experimental groups were identified using microarray profiling. The levels of DE mRNAs and lncRNAs were measured by reverse transcription­quantitative PCR (RT­qPCR). Furthermore, Gene Ontology (GO) and pathway enrichment analyses of DE mRNAs and lncRNAs were performed. To identify core regulatory factors among DE lncRNAs and mRNAs, a lncRNA­mRNA network was constructed. A total of 357 DE lncRNAs and 542 DE mRNAs between the LPS­treated and untreated groups were identified (fold-change >1.5; P<0.05). In addition, selected microarray data were confirmed by RT­qPCR. GO analysis of the DE mRNAs indicated that the biological functions of the upregulated mRNAs included inflammatory response, immune response, metabolic process and signal transduction, whereas those of the downregulated mRNAs were metabolic process, cell cycle, apoptosis and inflammatory response. In addition, pathway enrichment analysis of the upregulated mRNAs revealed that the most enriched pathways were the NF­κB signaling pathway, B­cell receptor signaling pathway and apoptosis, while the downregulated mRNAs were significantly involved in metabolic pathways, the phosphatidylinositol signaling system, cytokine­cytokine receptor interaction and the Toll­like receptor signaling pathway. The lncRNA­mRNA co­expression network suggested that lncRNAs NONMMUT024673 and NONMMUT062258 may have an important role in LPS­induced intestinal macrophages. The present study identified the DE profiles between LPS­ and non­LPS­treated intestinal macrophages. These DE lncRNAs and mRNAs may be used as potential targets for attenuating excessive inflammatory response in intestinal mucosal barrier dysfunction.

LncRNA SNHG15 Contributes to Immuno-Escape of Gastric Cancer Through Targeting miR141/PD-L1.

INTRODUCTION: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in many biological processes and severs as important regulators during the progression of gastric cancer. METHODS: Here, we introduced human lncRNA SNHG15 which was highly expressed in gastric cancer and cells. Interestingly, the expression of SNHG15 was correlated with programmed cell death ligand 1 (PD-L1), which promotes the resistance of gastric cancer cells to immune responses. Meanwhile, SNHG15 downregulation suppressed the expression of PD-L1 and resistance of immune responses. RESULTS: Further, our results suggested that SNHG15 acted as a competing endogenous RNA (CeRNA) to sponge miR-141, which was downregulated in gastric cancers and negatively correlated to PD-L1. CONCLUSION: Our results suggested that SNHG15 improved the expression of PD-L1 by inhibiting miR-141, which in turn promoted the resistance of stomach cancer cells to the immune responses.

Netrin-1 promotes cell neural invasion in gastric cancer via its receptor neogenin.

Neural invasion (NI) is one of the important routes for local spread of gastric cancer (GC) correlated with poor prognosis. However, the exact cellular characteristics and molecular mechanisms of NI in GC are still unclear. Netrin-1(NTN1) as an axon guidance molecule was firstly found during neural system development. Importantly, NTN1 has an essential role in the progression of malignant tumor and specifically mediates the induction of invasion. In this study, we found NTN1 expression was significantly increased in 97 tumor tissues from GC patients and positively correlated with NI (p<0.05). In addition, we detected NTN1 knockdown significantly suppressed GC cells migration and invasion. Moreover, our results showed that reciprocity was observed between GC cells and neurites colonies in dorsal root ganglia (DRG)-GC cells co-culture vitro model. GC cells with NTN1 silencing could suppress their abilities to navigate along surrounding neuritis and this effect was depended on its receptor neogenin. In vivo, NTN1 inhibition also decreased GC cells sciatic nerve invasion. Taken together, our findings argue that NTN1 and its receptor neogenin might act synergistically in promoting GC cells neural invasion. Inhibiting the activity of NTN1 could be a potential strategy targeting NI in GC therapy.

G-protein-signaling modulator 2 expression and role in a CD133+ pancreatic cancer stem cell subset.

BACKGROUND: To investigate the expression and role of G-protein-signaling modulator 2 (GPSM2) in a CD133+ pancreatic stem cell subset. MATERIALS AND METHODS: Pancreatic cancer stem cells (PCSCs) from the cell line PANC-1 were sorted into CD133+ and CD133- subsets by flow cytometry. The tumorigenic potential of the subsets was assessed by subcutaneous tumor formation experiments in nude mice. Differential expression of GPSM2 was examined by real-time quantitative-PCR (qPCR) and Western blotting. To silence GPSM2 expression, a shRNA lentiviral vector targeting GPSM2 was constructed and stably transfected into CD133+ PCSCs. The inhibitory efficiency of the GPSM2 gene was verified by qPCR and Western blotting. The proliferation, colony formation, and migration abilities of the transfected CD133+ pancreatic cancer cells were assessed by MTT, soft agar colony formation, and Transwell assays. RESULTS: CD133+ and CD133- cell subsets were successfully isolated from PANC-1 cells. The CD133+ subset subcutaneously formed tumors in nude mice that were significantly bigger (343.05±57.59 mm3 vs 176.86±32.58 mm3, P<0.01) and denser (4.13±0.37 g vs 1.07±0.21 g, P<0.01) than those of the CD133- group. The GPSM2 mRNA and protein expression was significantly higher in CD133+ cells than in CD133- cells. Stable downregulation of GPSM2 expression reduced the proliferation, colony formation, and migration abilities of CD133+ PANC-1 cells (P<0.05). CONCLUSION: The CD133+PANC-1 cells have obvious stem cell characteristics and increased GPSM2 expression. Downregulation of GPSM2 significantly reduces the proliferation and migration ability of the cells. Therefore, GPSM2 may provide an important target for regulating PCSCs.

MicroRNA-505 suppresses gastric cancer cell proliferation and invasion by directly targeting Polo-like kinase-1.

PURPOSE: The expression of microRNA-505 (miR-505) has been investigated in various cancers; however, its effect and mechanism in relation to gastric cancer (GC) are yet to be determined. Thus, the current evaluation aimed to examine the expression and potential role of miR-505 in GC. MATERIALS AND METHODS: Quantitative real-time PCR was carried out to analyze miR-505 expression in GC cells and tissues. We observed that miR-505 is differentially expressed in GC cells following transfection of its mimics or inhibitors. Changes in cell invasion, cell proliferation, and epithelial-mesenchymal transition markers were measured. RESULTS: These findings indicated that miR-505 expression is downregulated in both GC cell lines and GC tissues. In addition, knockdown miR-505 induced the invasion and proliferation of GC cells. Transfection of miR-505 mimics led to an elevation in N-cadherin expression but a decrease in E-cadherin expression. Furthermore, we have shown that miR-505 binds to the 3'-UTR region of Polo-like kinase-1. CONCLUSION: Our results indicated that miR-505 suppresses GC cell proliferation and invasion; it may be a valuable candidate gene for seeking therapy strategy for GC.

[Corrigendum] Netrin­1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation.

During the preparation of the figures in the above article, the authors inadvertently selected images for the shCTL experiments portrayed in Fig. 5I and J (for the MGC803 and SGC7901 cell lines, respectively) that were generated from the same original data source. A corrected version of Fig. 5 is shown opposite, showing the correct data for the shCTL experiment performed in SGC7901 cells (Fig. 5J). This error did not affect the major conclusions reported in the paper. All the authors have agreed to this Corrigendum. The authors regret this error, and apologize for any confusion that it may have caused. [the original article was published in Oncol Rep 40: 2325­2333, 2018; DOI: 10.3892/or.2018.6614].

PLK1 as a potential prognostic marker of gastric cancer through MEK-ERK pathway on PDTX models.

BACKGROUND: PLK1 has been identified as having a great effect on cell division and maintaining genomic stability in mitosis, spindle assembly, and DNA damage response by current studies. MATERIALS AND METHODS: We assessed PLK1 expression in cervical cancer tissues and cells. We have also evaluated the effects of PLK1 on gastric cancer cell proliferation, migration, and apoptosis both in vitro and in vivo. RESULTS: Our results show that PLK1 is overexpressed in gastric cancer tissues and cells. Inhibition of PLK1 contributes cell cycle G2-phase arrest and inhibits the proliferation, migration, and apoptosis of gastric cancer (GC) cells, whereas its overexpression promotes proliferation, migration, and apoptosis in these cells. Moreover, PLK1 inhibition reduces expression of pMEK and pERK. More importantly, in vivo by analyzing tumorigenesis in patient-derived tumor xenograft (PDTX) models, the inhibition of PLK1 activity by BI6727 significantly decreased the volume and weight of the tumors compared with control group (P<0.01). CONCLUSION: Our results found that PLK1 has a significant impact on the survival of GC cells; it may become a prognostic judge, a potential therapeutic target, and a preventative biomarker of GC.

Netrin­1 induces the proliferation of gastric cancer cells via the ERK/MAPK signaling pathway and FAK activation.

Netrin­1 (NTN1) has been demonstrated to promote tumorigenesis in multiple types of cancer; however, its role in the growth of gastric cancer (GC) cells has not been described in detail. In the present study, the data suggested that NTN1 knockdown significantly decreased the proliferation of GC cells, whereas NTN1 overexpression had an opposing effect. Furthermore, the use of focal adhesion kinase (FAK) inhibitor decreased the proliferation of GC cells. It was also revealed that NTN1 markedly induced the phosphorylation of FAK, extracellular signal­regulated kinase (ERK) and c­Jun N­terminal kinase (JNK), but did not induce the phosphorylation of P38. In addition, the expression of ERK and JNK was markedly inhibited by treatment with FAK inhibitor. Xenograft analysis using GC cells revealed that NTN1 overexpression promoted tumor growth. Furthermore, the expression of NTN1 in samples collected from nude mice was downregulated in the NTN1 knockdown group and upregulated in the NTN1 overexpression group compared with the control short hairpin RNA group. These results suggest that NTN1­induced GC cell proliferation is mediated by activating ERK/MAPK signaling cascades via the distinct activation of FAK.

Comparison between uncut Roux-en-Y and Roux-en-Y reconstruction after distal gastrectomy for gastric cancer: A meta-analysis.

AIM: To compare uncut Roux-en-Y (U-RY) gastrojejunostomy with Roux-en-Y (RY) gastrojejunostomy after distal gastrectomy (DG) for gastric cancer. METHODS: A literature search was conducted in Pubmed, Embase, Web of Science, Cochrane Library, Science Direct, Chinese National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Database to identify studies comparing U-RY with RY after DG for gastric cancer until the end of December 2017. Pooled odds ratio or weighted mean difference with 95% confidence interval was calculated using either fixed- or random-effects models. Perioperative outcomes such as operative time, intraoperative blood loss, and hospital stay; postoperative complications such as anastomotic bleeding, stricture and ulcer, reflux gastritis/esophagitis, delayed gastric emptying, and Roux stasis syndrome; and postoperative nutritional status (serum hemoglobin, total protein, and albumin levels) were the main outcomes assessed. Meta-analyses were performed using RevMan 5.3 software. RESULTS: Two randomized controlled trials and four nonrandomized observational clinical studies involving 403 and 488 patients, respectively, were included. The results of the meta-analysis showed that operative time [weighted mean difference (WMD): -12.95; 95%CI: -22.29 to -3.61; P = 0.007] and incidence of reflux gastritis/esophagitis (OR: 0.40; 95%CI: 0.20-0.80; P = 0.009), delayed gastric emptying (OR: 0.29; 95%CI: 0.14-0.61; P = 0.001), and Roux stasis syndrome (OR: 0.14; 95%CI: 0.04-0.50; P = 0.002) were reduced; and the level of serum albumin (WMD: 0.71; 95%CI: 0.24-1.19; P = 0.003) was increased in patients undergoing U-RY reconstruction compared with those undergoing RY reconstruction. No differences were found with respect to intraoperative blood loss, hospital stay, anastomotic bleeding, anastomotic stricture, anastomotic ulcer, the levels of serum hemoglobin, and serum total protein. CONCLUSION: U-RY reconstruction has some clinical advantages over RY reconstruction after DG.

Netrin-1 promotes metastasis of gastric cancer by regulating YAP activity.

Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect. We also demonstrated that netrin-1 upregulated YAP expression via its transmembrane receptor neogenin. Furthermore, our in vitro and in vivo results showed that the effect of netrin-1 on GC cells migration and invasion abilities was regulated by YAP. Collectively, our results defined netrin-1 as a positive regulator of malignant tumor metastasis in GC by activating the YAP signaling, with potential implications for new approaches to GC therapy.

Giant mucinous adenocarcinoma of the appendix: a case report.

BACKGROUND: Appendiceal mucinous adenocarcinoma is an extremely rare disease in clinical practice. Here, we report a case of unprecedented size that occupied the entire abdomen of a man. CASE PRESENTATION: A 49-year-old Chinese Han man presented with symptoms of abdominal distension. During a computed tomography imaging examination, a cystic-solid mass that occupied his entire abdominal cavity was detected. During exploratory laparotomy, an appendiceal tumor in his abdominal-pelvic cavity measuring 27.6 × 14.2 cm was found, and he underwent tumor resection. The pathology of the tumor identified a well-differentiated appendiceal mucinous adenocarcinoma with mucin infiltrating into the soft tissue of the lump edge and omentum tissue. After surgery, our patient accepted intraperitoneal infusion chemotherapy. At present, he has had no recurrence for 15 months. CONCLUSIONS: To the best of our knowledge, the present case is the largest appendiceal mucinous adenocarcinoma reported. Surgical tumor resection is the preferred treatment for appendiceal mucinous adenocarcinoma. This is supplemented by chemotherapy which can further prolong survival.

[Interferon regulatory factor 5(IRF5) regulates the differentiation of bone marrow-derived macrophages in mice].

Objective: To investigate the expression differences of interferon regulatory factor 5( IRF5) between M1 and M2 macrophages derived from mouse bone marrow and the effects of small interfering RNA targeting IRF5 gene( IRF5siRNA) on macrophage differentiation. Methods: With the treatment of IFN-γ and lipopolysaccharide( LPS),mouse bone marrow-derived macrophages were differentiated into M1 macrophages; while with the treatment of IL-4,mouse bone marrow-derived macrophages were differentiated into M2 macrophages. Differentiation efficiency was measured by flow cytometry. The expressions of IRF5,IL-12,tumor necrosis factor-α( TNF-α),inducible nitric oxide synthase( i NOS),arginase 1( Arg1),macrophage mannose receptor( MMR) mRNAs in M1 and M2 macrophages were analyzed by quantitative real-time PCR( RT-PCR). Furthermore,macrophages were infected with IRF5 siRNA,and then the mRNA expressions of the above proteins in M1 and M2 were tested by RT-PCR,and the protein expressions were detected by Western blotting.The results were analyzed to evaluate the polarization state of macrophages. Results: The differentiation proportion of macrophages measured by flow cytometry was 81. 7%. RT-PCR showed that the expressions of IRF5,IL-12,i NOS mRNAs were obviously higher in M1 macrophages than in M2,and TNF-α mRNA was also higher in M1 macrophages. The expressions of Arg1,MMR mRNAs were obviously higher in M2 macrophages than in M1 macrophages. After silencing the IRF5 by IRF5 siRNA,the expressions of IRF5, IL-12, TNF-α and i NOS mRNAs decreased remarkably in macrophages, while the expressions of Arg-1,MMR mRNAs increased. Western blotting revealed that the expressions of IRF5,IL-12,TNF-α and i NOS proteins were significantly reduced,while the expressions of Arg1 and MMR protein were raised. The polarization of macrophages shifted to M2 state. Conclusion: IRF5 can be used as an important marker to identify M1 and M2 macrophages,and it has an important role in the regulation of macrophage differentiation.

Study on the related factors of lymph node detection number in rectal cancer patients underwent laparoscopic surgery / 中国内镜杂志

Objective To investigate the related factors of lymph node detection number in rectal cancer patients underwent laparoscopic surgery. Methods 98 patients with rectal cancer who underwent laparoscopic surgery were selected from January 2014 to January 2010. All the patients general information [gender, age, body mass index (BMI)], preoperative imaging findings and pathological data (tumor size, gross type, TNM stage, distant metastasis, histological differentiation and depth of invasion, et al), surgery related data (experience of surgeon, operation time) and preoperative radiotherapy and chemotherapy were collected. Results The age, BMI, tumor size, length of specimen, invasive depth, surgeon and preoperative radiotherapy and chemotherapy was correlated with the number of lymph nodes in patients with laparoscopic surgery (P < 0.05), but gender, TNM staging, general type, histological differentiation, operation time were not associated with the number of lymph nodes detected in minimally invasive surgery for rectal cancer (P > 0.05). Multiple linear regression analysis showed that BMI, tumor size, length of specimen, invasive depth, surgeon and preoperative radiotherapy and chemotherapy were the independent influencing factors of lymph node detection in patients with minimally invasive rectal cancer (P < 0.05). Conclusion The factors of patients, tumor status, surgical factors and preoperative chemoradiotherapy are related to the number of lymph nodes in patients with rectal cancer.

IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitis in vitro.

AIM: To investigate the role of interferon regulatory factor 5 (IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis (SAP) in vitro. METHODS: A mouse SAP model was established by intraperitoneal (ip) injections of 20 µg/kg body weight caerulein. Pathological changes in the lung were observed by hematoxylin and eosin staining. Lung macrophages were isolated from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages were detected by fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction (RT-PCR). They were treated with IL-4/IRF5 specific siRNA (IRF5 siRNA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RT-PCR. RESULTS: SAP associated acute lung injury (ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siRNA reversed the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siRNA vs S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P < 0.01), TNF-α (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.019 ± 0.018, P < 0.001), iNOS (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.026 ± 0.018, P < 0.001) and IL-12 (S + IRF5 siRNA vs S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P < 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10 (S + IRF5 siRNA vs S + PBS, 0.060 ± 0.055 vs 0.0230 ± 0.018, P < 0.01) and Arg-1 (S + IRF5 siRNA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P < 0.001), were increased. IRF5 siRNA could reverse the lung macrophage polarization more effectively than IL-4. CONCLUSION: Treatment with IRF5 siRNA can reverse the pancreatitis-induced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI.

CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma.

Overactivation of Ras signaling is very common in the hepatocellular carcinoma (HCC) due to its constitutive active mutation, which makes it a big challenge to target Ras signaling. Therefore, identifying effectors downstream of Ras signaling would benefit the development of novel therapeutic strategies. In this study, it was found that the expression of CARF (collaborate of ARF) was induced by oncogenic RasV12. The expression of CARF was up-regulated in both HCC mouse model (Alb-Cre; P53f/f; Loxp-Stop-Loxp-RasG12D) and human HCC clinical samples. Overexpression of CARF promoted the growth and migration of HCC cells, while knocking down the expression of CARF inhibited the growth and migration of HCC cells. In the mechanism study, CARF was found to interact with beta-catenin, impaired the interaction between beta-catenin and ICAT, and activated beta-catenin/TCF signaling. Moreover, knocking down the expression of CARF inhibited the tumorigenesis in the HCC mouse model. Taken together, this study revealed the oncogenic functions of CARF in the tumorigenesis of HCC by activating beta-catenin/TCF signaling, and suggested CARF might be a therapeutic target in the treatment of HCC.