Effect of Compressive Modulus of Porous PVA Hydrogel Coating on the Preventing Adhesion of Polypropylene Mesh.

PP mesh is a widely used prosthetic material in hernia repair. However, visceral adhesion is one of the worst complications of this operation. Hence, an anti-adhesive PP mesh is developed by coating porous polyvinyl alcohol (PVA) hydrogel on PP surface via freezing-thawing process method. The compressive modulus of porous PVA hydrogel coating is first regulated by the addition of porogen sodium bicarbonate (NaHCO3) at various quality ratios with PVA. As expected, the porous hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro tests demonstrate the modified PP mesh show superior coating stability, excellent hemocompatibility, and good cytocompatibility. In vivo experiments illustrate that PP mesh coated by the PVA4 hydrogel that mimicked the modulus of native abdominal wall could prevent adhesion effectively. Based on this, the rapamycin (RPM) is loaded into the porous PVA4 hydrogel coating to further improve anti-adhesive property of PP mesh. The Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining results verified that the resulting mesh could alleviate the inflammation response and reduce the deposition of collagen around the implantation zone. The biomimetic mechanical property and anti-adhesive property of modified PP mesh make it a valuable candidate for application in hernioplasty.

Polypropylene mesh coated with hyaluronic acid/polyvinyl alcohol composite hydrogel for preventing bowel adhesion.

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.

Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis.

OBJECTIVES: This study aimed to determine the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-EXO) on atherosclerosis (AS), and its related underlying mechanisms. METHODS: Exosomes were isolated from mouse BMSCs, and identified by transmission electron microscopy (TEM), Nanosight (NTA), and western blot. A mouse AS model was established, and exosomes were injected into the tail vein. Total cholesterol (TC) and triglycerides (TG) were detected using their corresponding assay kits. The contents of IL-1ß and IL-18 in serum were detected by ELISA. The mRNA and protein expression levels of GSDMD, Caspase1, and NLRP3 were detected by qRT-PCR and Western blot. Finally, aortic tissues in the Model and BMSC-EXO groups were sent for sequencing. RESULTS: TEM, NTA, and western blot indicated successful isolation of exosomes. Compared with the control group, the TC, TG contents, IL-1ß and IL-18 concentrations of the mice in the Model group were significantly increased; nonetheless, were significantly lower after injected with BMSC-EXO than those in the Model group (p < 0.05). Compared with the control group, the expressions of NLRP3, caspase-1 and GSDMD were significantly up-regulated in the Model group (p < 0.05), while the expressions of NLRP3, caspase-1, and GSDMD were significantly down-regulated by BMSC-EXO. By sequencing, a total of 3852 DEGs were identified between the Model and BMSC-EXO group and were significantly enriched in various biological processes and pathways related to mitochondrial function, metabolism, inflammation, and immune response. CONCLUSION: AS can induce pyroptosis, and BMSC-EXO can reduce inflammation and alleviate the progression of AS by inhibiting NLRP3/Caspase-1/GSDMD in the pyroptosis pathway.

Placement of Bare Self-Expanding Metal Stent for Isolated Superior Mesenteric Artery Dissection.

BACKGROUND: To evaluate the safety and efficacy of placing bare self-expanding metal stent (SEMS) for treating isolated superior mesenteric artery dissection (ISMAD). METHOD: Patients with ISMAD who received bare SEMS from January 2014 to December 2021 at the authors' center were included. Baseline characteristics, clinical manifestation, radiological findings, and treatment outcomes, including symptom relief and SMA remodeling, were analyzed. RESULT: A total of 26 patients were included in this study. Among the patients, 25 were admitted due to persistent abdominal pain, and 1 was admitted based on computed tomography angiography (CTA) during physical examination. According to CTA scan, the percentage of stenosis was 91% (53.8-100%), and the length of dissection was 100.2 ± 8.4 mm. All patients received bare SEMS placement. The median time to symptom relief was 1 day (interquartile range, 1 3 days). The the median follow-up time of CTA was 6.8 months (range, 2-85 months), with an average of 16.2 months. Complete remodeling of the superior mesenteric artery (SMA) was recorded in 24 patients. The median time to remodeling was 3 months with an average of 4.7 months. Survival analysis indicated no significance difference in remodeling time between different ISMAD types based on Yun classification (P = 0.888) or between acute and nonacute disease (P = 0.423). Incomplete remodeling was noted in 2 patients. Distal stent occlusion without SMA-related symptoms was seen in 1 patient. Proximal stent stenosis occurred in 1 patient, and restenting was performed. The median follow-up time by telephone was 20.8 (4-91.5) months, and no intestinal ischemic symptoms were observed in any patient. CONCLUSIONS: Bare SEMS placement can effectively relieve SMA-related symptoms in a short time and promote dissection remodeling in ISMAD. Time from symptom onset and classification of ISMAD seem not to have effects on SMA remodeling after bare SEMS placement.

A Novel Prognostic Biomarker CCR8 for Gastric Cancer and Anti-CCR8 Blockade Attenuate the Immunosuppressive Capacity of Tregs In Vitro.

Objective: To investigate the immunotherapeutic roles and functions of C-C Motif Chemokine Receptor 8 (CCR8) molecule in gastric cancer (GC). Materials and Methods: Clinicopathological features of 95 GC cases were collected by a follow-up survey. The expression level of CCR8 was measured by immunohistochemistry (IHC) staining and analyzed with the cancer genome atlas database. The relationship between CCR8 expression and Clinicopathological features of GC cases was evaluated by univariate and multivariate analysis. Flow cytometry was used to determine the expression of cytokines and the proliferation of CD4+ regulator T cells (Tregs) and CD8+ T cells. Results: An upregulated expression of CCR8 in GC tissues was associated with tumor grade, nodal metastasis, and overall survival (OS). Tumor-infiltrated Tregs with higher expression of CCR8 produced more IL10 molecules in vitro. In addition, anti-CCR8 blocking downregulated IL10 expression produced by CD4+ Tregs, and reversed the suppression by Tregs on the secretion and proliferation of CD8+ T cells. Conclusion: CCR8 molecule could be a prognostic biomarker for GC cases and a therapeutic target for immune treatments.

Prognostic Impact of Aberrantly Expressed Protein-coding Gene Associated With Gastric Cancer's Regulatory T Cells, Based on Online Databases.

Context: Gastric cancer (GC) remains one of the most prevalent malignancies worldwide, and no effective cure exists for advanced GC. Clinicians believe that molecularly targeted therapy through PCGs may replace surgery, radiotherapy, and other treatments as a breakthrough in curing malignancies. Objective: The study intended to examine the impact of aberrant expression of the protein-coding genes (PCGs) associated with regulatory T cells on the prognosis of patients with gastric cancer (GC). Design: The research team performed a genetic study through research of genetic data in online databases. Setting: The study took place at Zhongda Hospital. Outcome Measures: The research team selected a publicly available dataset, genetic suppressor element 109476 (GSE109476), from the Gene Expression Omnibus (GEO) database for differential gene analysis, gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for PCGs associated with regulatory T cells as well as the Gene Expression Profiling Interactive Analysis (GEPIA) database with the Kaplan-Meier Plotter database to analyze the expression of the above PCGs in GC and the prognostic impact on GC. Results: The GEO2R analysis found 315 differentially expressed PCGs in GSE109476, among which nine PCGs were associated with regulatory T cells: (1) chemokine (C-C motif) ligand 19 (CCL19), (2) CCL21, (3) C-C chemokine receptor type 7 (CCR7), (4) cluster of differentiation 70 (CD70), (5) ephrin B3 (EFNB3), (6) early growth response 3 (EGR3), (7) interleukin-7 receptor (IL7R), (8) galectin-1 (LGALS1), and (9) tumor necrosis factor (TNF) receptor superfamily member 13C (TNFRSF13C). The GEPIA database indicated that no significant differences existed between the expression of CCL19, CCL21, CD70, EFNB3, EGR3, IL7R, and TNFRSF13C in stomach adenocarcinoma (STAD) tissues and that in normal tissues (P > .05), while expressions of CCR7 and LGALS1 were significantly elevated in STAD tissues compared to the normal tissues (P < .05). The Kaplan-Meier Plotter database analysis, on the other hand, showed a significant relationship between all of the above-mentioned PCGs, except CCL19, and the prognosis of GC. Conclusions: CCL19, CCL21, CCR7, CD70, EFNB3, EGR3, IL7R, LGALS1, and TNFRSF13C are PCGs are differentially expressed in GC and closely associated with regulatory T cells. They may affect the occurrence and development of GC through a variety of pathways, including regulation of immune infiltration and inflammation, and are of great potential research value.

Polypropylene composite hernia mesh with anti-adhesion layer composed of PVA hydrogel and liposomes drug delivery system.

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA10-c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA10-c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA10-c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA10-c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA10-c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA10-c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA10-c-PP might be a potential candidate for anti-adhesion treatment. DATA AVAILABILITY: Data will be made available on request.

Corrigendum: Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids.

[This corrects the article DOI: 10.3389/fbioe.2022.917726.].

Activation of the NFκB signaling pathway in IL6+CSF3+ vascular endothelial cells promotes the formation of keloids.

Background: Keloid is a disease caused by abnormal proliferation of skin fibres, the causative mechanism of which remains unclear. Method: In this study, endothelial cells of keloids were studied using scRNAseq combined with bulk-RNAseq data from keloids. The master regulators driving keloid development were identified by transcription factor enrichment analysis. The pattern of changes in vascular endothelial cells during keloid development was explored by inferring endothelial cell differentiation trajectories. Deconvolution of bulkRNAseq by CIBERSORTX verified the pattern of keloidogenesis. Immunohistochemistry for verification of the lesion process in keloid endothelial cells. Results: The endothelial cells of keloids consist of four main cell populations (MMP1+ Endo0, FOS + JUN + Endo1, IL6+CSF3+Endo2, CXCL12 + Endo3). Endo3 is an endothelial progenitor cell, Endo1 is an endothelial cell in the resting state, Endo2 is an endothelial cell in the activated state and Endo0 is an endothelial cell in the terminally differentiated state. Activation of the NFΚB signaling pathway is a typical feature of Endo2 and represents the early skin state of keloids. Conclusion: We have identified patterns of vascular endothelial cell lesions during keloidogenesis and development, and have found that activation of the NFΚB signaling pathway is an essential feature of keloid formation. These findings are expected to contribute to the understanding of the pathogenesis of keloids and to the development of new targeted therapeutic agents for the lesional characteristics of vascular endothelial cells.

Polypropylene mesh combined with electrospun poly (L-lactic acid) membrane in situ releasing sirolimus and its anti-adhesion efficiency in rat hernia repair.

This study developed, a novel polypropylene (PP) mesh combined with poly (L-lactic acid) (PLA) electrospun nanofibers loaded sirolimus (SRL). The PP mesh was combined with PLA/SRL (1/0, 1/0.01, 1/0.02; mass ratios) composed electrospun membrane characterized by FTIR spectroscopy, XPS and SEM, and evaluated for cytocompatibility in vitro. In an in vivo study, a total of 84 Sprague-Dawley rats were employed to evaluate the efficacy of the novel composite PP mesh anti-adhesion, mechanical properties and inflammation. As a results, the PLA/SRL membrane could compound with PP mesh stably and load SRL. Although tensile testing showed that the mechanical properties of composite mesh decreased in vivo, the integration strength between the tissue and mesh was still able to counteract intra-abdominal pressure. Compared with the native PP mesh group, the novel PP mesh group showed a lower score for abdominal adhesion and inflammation. More importantly, the novel PP mesh completely integrated with the abdominal wall and had sufficient mechanical strength to repair abdominal wall defects.

Long-Term Follow-Up of Lichtenstein Repair of Inguinal Hernia in the Morbid Patients With Self-Gripping Mesh (ProgripTM).

Objective: This study aimed to demonstrate the safety and the efficacy of the self-gripping mesh (ProgripTM) for inguinal hernia repair in morbid patients of the higher American Society of Anesthesiologists (ASA) classification (ASA III and IV). The incidence of chronic pain, postoperative complications, and hernia recurrence was evaluated. Methods: Data were collected retrospectively from the files of the patient and were analyzed for 198 hernias in 147 patients. All the patients included in this study had undergone inguinal hernia repair by Lichtenstein approach with the self-gripping mesh (ProgripTM) in the same clinical center. Preoperative, perioperative, and postoperative data were collected and a long-term follow-up of 31.8 ± 19.5 m (5-60 m) was performed. Complications, pain scored on a 0-10 numeric rating scale (NRS), and hernia recurrence were assessed. Results: During the past 5 years, 198 hernias in 147 patients were repaired with the Lichtenstein procedure with the self-gripping mesh (ProgripTM). The majority of the patients were high level of the ASA classification (ASA III and IV) (95.9%), with ASA III (10.2%) and IV (85.7%). The mean operation time was 71.2 ± 23.8 min. The mean length of postoperative stay was 2.5 ± 2.1 days. There were no intraoperative complications. About 14 cases (7.1%) suffered from postoperative surgical wound complications, which were limited to the skin and subcutaneous tissue and were cured with the conservative methods successfully; there was no mesh infection, the acute postoperative pain was low or mild [visual analog scale (VAS) score ≤ 4] and the chronic postoperative pain was reported in three patients (1.5%) and tolerable, hernia recurrence (femoral hernia recurrence) occurred in one patient half a year after during the follow-up period. Conclusion: This study demonstrated the advantages of the self-gripping mesh in hernia repair of the high-risk patients with inguinal hernia (ASA III and IV) by Lichtenstein procedure under local anesthesia.

Patient-centered developments in colon- and rectal cancer with a multidisciplinary international team: From translational research to national guidelines.

Rarely, scientific developments centered around the patient as a whole are published. Our multidisciplinary group, headed by gastrointestinal surgeons, applied this research philosophy considering the most important aspects of the diseases "colon- and rectal cancer" in the long-term developments. Good expert cooperation/knowledge at the Comprehensive Cancer Center Ulm (CCCU) were applied in several phase III trials for multimodal treatments of primary tumors (MMT) and metastatic diseases (involving nearly 2000 patients and 64 centers), for treatment individualization of MMT and of metastatic disease, for psycho-oncology/quality of life involving the patients' wishes, and for disease prevention. Most of the targets initially were heavily rejected/discussed in the scientific communities, but now have become standards in treatments and national guidelines or are topics in modern translational research protocols involving molecular biology for e.g., "patient centered individualized treatment". In this context we also describe the paths we had to tread in order to realize our new goals, which at the end were highly beneficial for the patients from many points of view. This description is also important for students and young researchers who, with an actual view on our recent developments, might want to know how medical progress was achieved.

Bilobalide Alleviated Dextran Sulfate Sodium-Induced Experimental Colitis by Inhibiting M1 Macrophage Polarization Through the NF-κB Signaling Pathway.

Bilobalide, a unique Ginkgo biloba constituent has attracted significant interest as a novel therapeutic option for neuronal protection. However, there is paucity of data on its effect on colitis. This work sought to evaluate the effect of bilobalide on macrophage polarization in vitro and dextran sulfate sodium (DSS) induced colitis in vivo. Through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/PI assay, it was shown that bilobalide has no significant toxicity on macrophage. Lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) induced macrophage activation and polarization were significantly suppressed by bilobalide as indicated by reduced expression of cytokine, major histocompatibility complex II (MHC-II), and CD11c. Pertinently, the signaling pathway study showed that the phosphorylation of p65 and its nuclear translocation were decreased while STAT1 was not affected. In DSS-treated mice, administration (i.g) of three doses of bilobalide na\mely 1.25 mg/kg (low dose group), 2.5 mg/kg (medium dose group), and 5 mg/kg (high dose group) was performed daily starting from day 1 to day 10. Medium and high dose bilobalide markedly reduced the inflammation of colitis proved via elevation of bodyweight, decrement in disease activity index (DAI), alleviation of colon damage as well as reduction in activity of colon tissue myeloperoxidase activity. In accordance with the in vitro results, the levels of inflammatory cytokines such as interleukin 6 (IL-6), IL-1ß, and tumor necrosis factor (TNF-α) in serum as well as messenger RNA (mRNA) expression in colon were obviously reduced in the bilobalide treated groups. Also, factor nuclear factor kappa B (NF-κB) signaling pathway was decreased significantly by bilobalide treatment. Collectively, these results indicated that administration of bilobalide improved experimental colitis via inhibition of M1 macrophage polarization through the NF-κB signaling pathway. Thus, bilobalide could act as a potential drug for the treatment of inflammatory bowel disease (IBD) in the not-too-distant future.

Low Pneumoperitoneum Pressure Improves Recovery of Transabdominal Preperitoneal Hernioplasty.

OBJECTIVE: To evaluate the recovery influence of CO2 pneumoperitoneum pressure for transabdominal preperitoneal hernioplasty (TAPP). STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: General Department II, Zhongda Hospital, Southeast University, Nanjing, China, from August 2016 to October 2018. METHODOLOGY: Eighty cases were enrolled prospectively and divided into three groups in chronological order. A 14 mmHg CO2 pressure was used for negative control group while the pressure was controlled at 12 mmHg for observation group and 10 mmHg for intervention group. General information included the patients' age, gender, type of hernia, hernia defect size, dissection of inguinal area, type of patch, time of operation, and frequency of swelling of perineum. Postoperative recovery was compared among the three groups at 24 hours and 1 month after surgery, including pain scores, foreign body sensation, local complications, urinary retention, swelling of the perineum, sex life and mobility. RESULTS: Seventy-eight patients were included in the final analysis. There were no differences among the three groups in patients' age, gender, type of hernia, hernia defect size, dissection of inguinal area and type of patch. However, the time of operation of intervention group increased (p=0.015) and incidence of swelling of perineum decreased than other two groups (p<0.05). After 24 hours, there were no significant differences in pain, foreign body sensation, local complications and urinary retention. Perineal swelling remission rate of intervention group was better than other two groups (p<0.05). After one month, three groups had no differences in the all terms of pain, foreign body sensation, sexual life and perineal swelling residual rate. CONCLUSION: Low pneumoperitoneum pressure can relieve swelling of perineum perioperatively and improve recovery of TAPP.

Combination of Polypropylene Mesh and in Situ Injectable Mussel-Inspired Hydrogel in Laparoscopic Hernia Repair for Preventing Post-Surgical Adhesions in the Piglet Model.

Polypropylene (PP) mesh has been used successfully for a long time in clinical practice as an impressive prosthesis for ventral hernia repair. To utilize a physical barrier for separating mesh from viscera is a general approach for preventing adhesions in clinical practice. However, a serious abdominal adhesion between the mesh and viscera can possibly occur post-hernia, especially with the small intestine; this can lead to a series of complications, such as chronic pain, intestinal obstruction, and fistula. Thus, determining how to prevent abdominal adhesions between the mesh and viscera is still an urgent clinical problem. In this study, a dopamine-functionalized polysaccharide derivative (oxidized-carboxymethylcellulose-g-dopamine, OCMC-DA) was synthesized; this was blended with carboxymethylchitosan (CMCS) to form a hydrogel (OCMC-DA/CMCS) in situ at the appropriate time. The physical and chemical properties of the hydrogel were characterized successfully, and its excellent biocompatibility was presented by the in vitro cell test. The combination of this hydrogel and PP mesh was used in laparoscopic surgery for repairing the abdominal wall defect, where the hydrogel could become fixed in situ on the PP mesh to form an anti-adhesion gel-mesh. The results showed that the gel-mesh could prevent abdominal adhesions effectively in the piglet model. Moreover, the histology and immunohistochemical staining proved that the gel-mesh could effectively alleviate the inflammation reaction and deposition of collagen around the mesh, and it did not disturb the integration between mesh and abdominal wall. Thus, the gel-mesh has superior tissue compatibility.

miR-532 promotes colorectal cancer invasion and metastasis by targeting NKD1.

The aim of this study was to investigate the effect of microRNA-532 (miR-532) on invasion and metastasis of colorectal cancer (CRC) cells, and the underlying mechanism. Human CRC cell line (HCT116) and normal colon (FHC) cells were used for this study. The cells were transfected with naked cuticle homolog 1 (NKD1) overexpression plasmid, miR-532 mimics, miR-532 inhibitor or miR-532 non-homologous sequence using lipofectamine 2000. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of miR-532 in CRC cells, and a combination of scratch and Transwell assays was used to assess the effect of miR-532 on migration and invasion of CRC cells. Western blotting was used to determine the effect of miR-532 on NKD1 expression in CRC cells. Bioinformatics analysis and luciferase reporter gene assay were used to assess the regulatory effect of miR-532 on NKD1. The expression of miR-532 was upregulated in CRC cells relative to normal colon cells (p < 0.05). The HCT116 cells transfected with miR-532 mimics migrated faster than those of miR-532 negative control (miR532-NC) group (p < 0.05). The migration ability of HCT116 cells transfected with miR-532 inhibitor was significantly reduced, when compared with that of miR532-NC group (p < 0.05). The invasive ability of HCT116 cells transfected with miR-532 mimics was significantly higher than that of miR532-NC cells (p < 0.05). However, inhibition of miR-532 expression significantly reduced the invasive ability of HCT116 cells (p < 0.05). Results of bioinformatics showed that miR-532 had specific binding sequence with the 3'UTR region of NKD1. After cloning the sequence into the luciferase reporter plasmid, miR-532 significantly inhibited the expression of NKD1 (p < 0.05). However, miR-532 had no inhibitory effect on mutated NKD1 3'UTR (p > 0.05). Results of Western blotting showed that increased miR-532 expression significantly reduced the expression of NKD1, while decreased miR-532 expression promoted the expression of NKD1 (p < 0.05). Overexpression of NKD1 significantly down-regulated miR-532 overexpression and promoted CRC cell invasion and metastasis (p < 0.05). miR-532 is highly expressed in CRC cells and directly inhibits NKD1 expression, while enhancing invasion and metastasis of CRC cells. It promotes the development of CRC by inhibiting the expression of NKD1.

RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression.

Breast cancer is one of the most common types of cancers which results in a high mortality rate for patients worldwide. In this study, we performed systematical experiments including tissue analysis (immunohistochemistry etc.) and cell functional experiments (cell counting assay, MTT assay, cell colony formation, cell migration assay, cell invasion assay etc.). We demonstrated that the expression level of RNA binding motif protein 3 (RBM3) was higher in human breast cancer tissues compared with adjacent non­tumor tissues. A high level of RBM3 was associated with worse post­operative relapse­free survival (RFS) and overall survival (OS) rates in patients with breast cancer. Among the patients with breast cancer, the expression of RBM3 was associated with patient lymph node metastasis and a high tumor grade. The knockdown of RBM3 markedly decreased the proliferation and metastasis of human breast cancer cells. In downstream pathway analysis, actin related protein 2/3 complex subunit 2 (ARPC2) was determined to be positively regulated by RBM3 through a post­transcriptional 3'UTR­binding manner. ARPC2 also played an oncogenic role and mediated the promoting role of RBM3 in the proliferation and metastasis of human breast cancer cells. Thus, on the whole, the findings of this study demonstrate that RBM3 acts as an oncogene in human breast cancer cells and that the functional depletion of RBM3 may be considered as a potential method for breast cancer therapy.