[Corrigendum] MYCN­amplified neuroblastoma cell­derived exosomal miR­17­5p promotes proliferation and migration of non­MYCN amplified cells.

Following the publication of this article, an interested reader drew to the authors' attention that the forward and reverse primer sequences written for GAPDH in Table I on p. 3 were incorrect. Upon requesting an explanation of these errors from the authors, they realized that these sequences had been written incorrectly in the paper: The sequence of the forward primer in Table I should have been written as 5'­CAG GAGGCATTGCTGATGAT­3', and the reverse primer should have been written as 5'­GAAGGCTGGGGCTCATTT­3'. The Editorial Office also requested seeing proof of purchase of the primers used in this study from the authors. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and all the authors agree with its publication. The authors also regret the inconvenience that these mistakes have caused. [Molecular Medicine Reports 23: 245, 2021; DOI: 10.3892/mmr.2021.11884].

Comparative study on three-dimensional versus two-dimensional imaging using a computer-assisted surgery system for preoperative planning in pediatric middle hepatic tumors.

BACKGROUD: The study objective was to compare three-dimensional and two-dimensional imaging using computer-assisted systems (CASs) in clinical guidance for preoperative surgical planning for middle hepatic tumors in children. METHODS: A retrospective analysis was performed on 23 children who underwent surgery for middle hepatic tumors in our hospital from January 2016 to June 2022. The surgical resection plan was formulated by the operator team using two-dimensional CT images before the operation. Then, the same qualified surgeons conducted an in-depth analysis and formulated the surgical resection scheme for the same pediatric patient using three-dimensional imaging of the middle hepatic tumor. The feasibility of the two schemes was compared and analyzed. RESULT: All the tumors were successfully removed according to the preoperative method developed using three-dimensional imaging. The postoperative short-term follow-up revealed that all patients were doing well. Preoperative plans were revised in 9 cases after evaluating the three-dimensional images due to the disparity between the original plans and the three-dimensional relationship between the tumor and blood vessels, vascular variation, and the volume of remnant liver. CONCLUSIONS: Three-dimensional imaging with a computer-assisted surgery system is superior to two-dimensional imaging in the preoperative planning of pediatric hepatoblastoma.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

Pancreatobiliary reflux increases macrophage-secreted IL-8 and activates the PI3K/NFκB pathway to promote cholangiocarcinoma progression.

BACKGROUND: Persistent pancreaticobiliary reflux (PBR) is associated with a high risk of biliary malignancy. This study aimed to evaluate the proportion of PBR in biliary tract diseases and mechanisms by which PBR promoted cholangiocarcinoma progression. METHODS: Overall 227 consecutive patients with primary biliary tract disease participated in this study. The amylase levels in the collected bile were analyzed. The mechanisms underlying the effect of high-amylase bile on bile duct epithelial and cholangiocarcinoma cells progression were analyzed. The source of interleukin-8 (IL-8) and its effects on the biological functions of cholangiocarcinoma cells were investigated. RESULTS: The bile amylase levels in 148 of 227 patients were higher than the upper serum amylase limit of 135 IU/L. PBR was significantly correlated with sex, pyrexia, and serum gamma-glutamyl transferase (GGT) levels in the patient cohort. High-amylase bile-induced DNA damage and genetic differences in the transcript levels of the gallbladder mucosa and facilitated the proliferation and migration of bile duct cancer cells (HUCCT1 and QBC939 cells). The concentration of many cytokines increased in high-amylase bile. IL-8 is secreted primarily by macrophages via the mitogen-activated protein kinase pathway and partially by bile duct epithelial cells. IL-8 promotes the progression of HUCCT1 and QBC939 cells by regulating the expression of epithelial-mesenchymal transition-associated proteins and activating the phosphatidylinositol 3-kinase/nuclear factor kappa-B pathway. CONCLUSIONS: PBR is one of the primary causes of biliary disease. IL-8 secreted by macrophages or bile duct epithelial cells stimulated by high-amylase bile promotes cholangiocarcinoma progression.

Cholangiocarcinoma identified in perforated choledochal cyst in a 3-year-old boy.

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.

Identifying a novel PHOX2B gene variant in a neuroblastoma family: A case report.

Neuroblastoma is a childhood cancer characterized by the formation of tumors derived from neuroblasts. Identifying the genetic mutations underlying neuroblastoma for genetic counseling and early diagnosis is essential. Thus, this study aimed to screen for pathogenic gene variants within a neuroblastoma family, aiming to contribute to genetic counseling practices. Clinical data was collected from a family affected by neuroblastoma, and peripheral blood DNA samples were obtained from all family members. A combination of whole-exome sequencing and Sanger sequencing was utilized to detect potential gene mutations. Proband 1 and her sister (Proband 2) were diagnosed with neuroblastoma, while their parents and siblings were unaffected. The analysis revealed a novel missense mutation, c.422G > A (p.Arg141Gln), in the PHOX2B gene, which was inherited from the mother. Notably, this mutation represents a previously unreported variant within the PHOX2B gene. Detecting the missense mutation c.422G > A (p.Arg141Gln) in the PHOX2B gene implies its potential pathogenic role within this neuroblastoma family. This finding widens the range of mutations observed in the PHOX2B gene and has important implications for early neuroblastoma diagnosis within this family.

Computer-assisted rescue of the inferior mesenteric artery in a child with a giant ganglioneuroblastoma: A case report.

BACKGROUND: Ganglioneuroblastoma (GNB) is a peripheral neuroblastoma (NB) with malignant degree between highly malignant NB and benign ganglioma (GN). Pathology is the gold standard of diagnosis. Although GNB is not uncommon in children, biopsy alone may lead to an inaccurate diagnosis, especially for giant tumors. However, surgical resection may be associated with significant complications. Here, we report a case of computer-assisted surgical resection of a giant GNB in a child and successful rescue of the inferior mesenteric artery. CASE SUMMARY: A 4-year-old girl was admitted to our department for a giant retroperitoneal lesion, which was considered to be an NB by her local hospital. The symptoms of the girl disappeared spontaneously without treatment. On physical examination, a mass of about 10 cm × 7 cm could be palpated in her abdomen. Ultrasonography and contrast-enhanced computed tomography performed in our hospital also showed an NB, and there was a very thick blood vessel inside the tumor. However, aspiration biopsy revealed GN. Surgical resection is the best treatment option for this giant benign tumor. For precise preoperative evaluation, three-dimensional reconstruction was performed. It was clear that the tumor was close to the abdominal aorta. The superior mesenteric vein was pushed forward, and the inferior mesenteric artery passed through the tumor. Because GN generally does not invade blood vessels, we split the tumor with a CUSA knife during the operation and found that there was indeed a straight and intact vascular sheath. Arterial pulsation was observed in the completely exposed inferior mesenteric artery. The pathologists interpreting the tissue finally diagnosed it as a mixed GNB (GNBi), which is more malignant than GN. However, both GN and GNBi usually have a good prognosis. CONCLUSION: This was a case of successful surgical resection of a giant GNB, and aspiration biopsy underestimated the pathological staging of the tumor. Preoperative three-dimensional reconstruction assisted with the radical resection of the tumor and rescue of the inferior mesenteric artery.

Application of computer-assisted surgery in pediatric mediastinal tumor surgery.

BACKGROUND: Computer-assisted Surgery system (CAS) is an effective medical imaging simulation tool, which is widely used in preoperative planning of surgery. The objective of this study is to investigate the clinical application of CAS in pediatric mediastinal tumor resection. METHODS: This retrospective study investigated 74 children who underwent mediastinal tumor resection between June 2008 and June 2022 at the pediatric surgical center of the Affiliated Hospital of Qingdao University and Qingdao Women and Children's Hospital. Preoperative chest computed tomography imaging was performed on all children. A total of 44 children (the CAS-assisted group) underwent clinical image 3D reconstruction and preoperative simulation using Hisense CAS. The control group consisted of 30 children who underwent a conventional procedure without CAS. The demographic, preoperative, and complication data were analyzed and compared between the two groups. t-test, Mann-Whitney U test, X2 test, or Fisher's exact test were used accordingly in this study during analysis. RESULTS: The median operative duration was 119.00 min in the CAS-assisted group and 140.50 min in the control group. The median intraoperative blood loss of the CAS-assisted group and the control group was 14.00 and 31.00 ml respectively. Relative to the control groups, the CAS-assisted group experienced shorter operative duration time (p = 0.041), and less intraoperative blood loss (p < 0.001). The difference in postoperative drain indwelling between the CAS-assisted group (median:4.00 days) and the control group (median:7.00 days) reached a statistical significance (p = 0.001). And the duration of hospitalization after the operation for the CAS-assisted group (median:7.00 days) was shorter than that for the control group (median:9.00 days) (p = 0.001). No significant difference could be found in the rate of blood transfusion (p = 0.258) and the incidence of postoperative complications (p = 0.719) between the two groups. CONCLUSION: Hisense CAS could effectively assist surgeons to clearly determine the anatomical site of tumors and provide accurate preoperative simulation for surgeons, so as to assist surgeons to specify effective surgical plans for patients.

miR-21 Targets Long Noncoding RNA PCAT29 to Promote Cell Proliferation in Neuroblastoma.

Long noncoding RNA (lncRNA) PCAT29 has been characterized as a tumor suppressor in several types of cancer, although its involvement in neuroblastoma (NB) is unknown. In this study, we analyzed the role of PCAT29 in NB. In paired NB and nontumor tissues from 56 patients with NB, microRNA (miR)-21 and PCAT29 expression was determined with reverse transcription quantitative PCR. Correlation between miR-21 and PCAT29 was evaluated with linear regression. The interaction between miR-21 and PCAT29 was predicted by the IntaRNA 2.0 program. In NB cells, miR-21 and PCAT29 were overexpressed to explore their relationship. In NB cell proliferation, the roles of miR-21 and PCAT29 were analyzed with propidium iodide staining and Ki67 staining assays. The results showed that PCAT29 was downregulated and miR-21 was upregulated in NB. MiR-21 was inversely correlated with PCAT29. RNA-RNA interaction prediction revealed that miR-21 might target PCAT29. MiR-21 overexpression reduced PCAT29 expression and increased NB cell proliferation, whereas PCAT29 overexpression inhibited NB cell proliferation. PCAT29 overexpression promoted NB cell apoptosis, while miR-21 overexpression inhibited NB cell apoptosis and attenuated PCAT29 overexpression-mediated NB cell apoptosis. In conclusion, MiR-21 may target PCAT29 to promote cell apoptosis in NB.

A Novel Multimodal Radiomics Model for Predicting Prognosis of Resected Hepatocellular Carcinoma.

Objective: To explore a new model to predict the prognosis of liver cancer based on MRI and CT imaging data. Methods: A retrospective study of 103 patients with histologically proven hepatocellular carcinoma (HCC) was conducted. Patients were randomly divided into training (n = 73) and validation (n = 30) groups. A total of 1,217 radiomics features were extracted from regions of interest on CT and MR images of each patient. Univariate Cox regression, Spearman's correlation analysis, Pearson's correlation analysis, and least absolute shrinkage and selection operator Cox analysis were used for feature selection in the training set, multivariate Cox proportional risk models were established to predict disease-free survival (DFS) and overall survival (OS), and the models were validated using validation cohort data. Multimodal radiomics scores, integrating CT and MRI data, were applied, together with clinical risk factors, to construct nomograms for individualized survival assessment, and calibration curves were used to evaluate model consistency. Harrell's concordance index (C-index) values were calculated to evaluate the prediction performance of the models. Results: The radiomics score established using CT and MR data was an independent predictor of prognosis (DFS and OS) in patients with HCC (p < 0.05). Prediction models illustrated by nomograms for predicting prognosis in liver cancer were established. Integrated CT and MRI and clinical multimodal data had the best predictive performance in the training and validation cohorts for both DFS [(C-index (95% CI): 0.858 (0.811-0.905) and 0.704 (0.563-0.845), respectively)] and OS [C-index (95% CI): 0.893 (0.846-0.940) and 0.738 (0.575-0.901), respectively]. The calibration curve showed that the multimodal radiomics model provides greater clinical benefits. Conclusion: Multimodal (MRI/CT) radiomics models can serve as effective visual tools for predicting prognosis in patients with liver cancer. This approach has great potential to improve treatment decisions when applied for preoperative prediction in patients with HCC.

Predictive factors for the surgical treatment of necrotizing enterocolitis in preterm infants: a single-center retrospective study.

BACKGROUND: Necrotizing enterocolitis (NEC) is a gastrointestinal disease that tends to occur in premature infants. Some features may be associated with an increased probability that preterm infants with NEC will require surgical treatment. This study aimed to identify the factors that increased the probability of surgical treatment in infants with NEC. METHODS: We retrospectively analyzed the data of premature infants with NEC who were hospitalized at The Affiliated Hospital of Qingdao University from April 2011 to April 2021. According to the treatments received, these patients were divided into medical NEC group and surgical NEC group. The perinatal characteristics, clinical manifestations, and laboratory values before the onset of NEC were subjected to univariate and multivariate analyses. RESULTS: A total of 623 preterm infants with NEC (> Bell's stage I) were included in this study, including 350 (56%) who received surgical treatment and 273 (44%) who received conservative medical treatment. Multivariate analysis showed that lower gestational age (P = 0.001, odds ratio (OR) (95% CI) = 0.91[0.86-0.96]), early occurrence of NEC (P = 0.003, OR (95% CI) = 0.86 [0.77-0.95]), hemodynamically significant patent ductus arteriosus (P = 0.003, OR (95% CI) = 7.50 [2.03-28.47]), and low serum bicarbonate (P = 0.043, OR (95% CI) = 0.863 [0.749-0.995]) were associated with an increased probability of surgical treatment in preterm infants with NEC. CONCLUSIONS: Our findings were applied to identify potential predictors for surgical treatment in preterm infants with NEC, which may facilitate early decisive management.

A Novel Method for Observing Tumor Margin in Hepatoblastoma Based on Microstructure 3D Reconstruction.

Objective: We investigated three-dimensional (3 D) reconstruction for the assessment of the tumor margin microstructure of hepatoblastoma (HB). Methods: Eleven surgical resections of childhood hepatoblastomas obtained between September 2018 and December 2019 were formalin-fixed, paraffin-embedded, serially sectioned at 4 µm, stained with hematoxylin and eosin (every 19th and 20th section stained with alpha-fetoprotein and glypican 3), and the digital images of all sections were acquired at 100× followed by image registration using the B-spline based method with modified residual complexity. Reconstruction was performed using 3 D Slicer software. Results: The reconstructed orthogonal 3 D images clearly presented the internal microstructure of the tumor margin. The rendered 3 D image could be rotated at any angle. Conclusions: Microstructure 3 D reconstruction is feasible for observing the pathological structure of the HB tumor margin.

Knockdown of long non-coding MIR210HG inhibits cell proliferation, migration, and invasion in hepatoblastoma via the microRNA-608-FOXO6 axis.

OBJECTIVE: Hepatoblastoma is the most common liver tumor. Recent research has found that long non-coding (lnc)RNAs are involved in multiple types of cancers, but the potential mechanism of lncRNA MIR210HG in hepatoblastoma remains unknown. The present study explored the molecular mechanism of MIR210HG in hepatoblastoma progression. METHODS: The cell counting kit-8 was used to detect cell viability, and Transwell assays assessed cell migration and invasion. Luciferase reporter assays showed the relationship between MIR210HG and microRNA (miR)-608 and between miR-608 and forkhead box O6 (FOXO6). Functional tests were verified in vivo by a tumor xenograft model. The expression of MIR210HG, miR-608, FOXO6, E-cadherin, N-cadherin, and vimentin was determined by quantitative reverse transcription polymerase chain reaction and western blotting. RESULTS: MIR210HG was shown to be highly expressed in hepatoblastoma tissues and cell lines. Knockdown of MIR210HG reduced proliferation, migration, and invasion in liver cancer cells, and suppressed tumor growth in vivo. MIR210HG competitively combined with miR-608, and miR-608 decreased FOXO6 expression. CONCLUSION: Our study demonstrated that knockdown of MIR210HG inhibits hepatoblastoma development through binding to miR-608 and downregulating FOXO6. Our results provide novel insights for hepatoblastoma treatment involving the MIR210HG-miR608-FOXO6 axis.

Application value of computer-assisted surgery system in pediatric hepatic hemangioma.

PURPOSE: To explore the treatment of pediatric hepatic hemangioma and the role of the Hisense computer-assisted surgery (Hisense CAS) system in diagnosis and treatment. METHODS: We collected the clinical and follow-up data of all pediatric hepatic hemangioma cases in our pediatric surgery department from March 2008 to March 2021 for retrospective analysis. The Hisense CAS system was used to create three-dimensional (3D) reconstructions based on computed tomography data. RESULTS: There were 71 patients, mainly infants (prenatal to 39 months). There were more males than females (42 vs. 29), and the alpha-fetoprotein level was significantly increased in 8 cases. 3D reconstruction by the Hisense CAS system showed that hepatic artery tracking was helpful for the differential diagnosis of pediatric hepatic hemangioma. Twenty-three children treated with propranolol showed significant differences in the tumour diameter, volume, and tumour-to-liver volume ratio after treatment (all P < 0.05). Compared with early surgical treatment, the curative effect of this approach was obvious. CONCLUSION: As a non-surgical treatment for symptomatic pediatric hepatic hemangioma, propranolol can replace surgical resection to a certain extent and reduce the proportion of children who need surgical intervention. Hisense CAS has advantages in evaluating the tumour volume before and after propranolol treatment. The liver volume and the liver tumour volume percentage provide new perspectives for evaluating the tumour outcome.

Trans-Ancestry Mutation Landscape of Hepatoblastoma Genomes in Children.

Hepatoblastoma (HB) is the most common malignant tumor in the liver of infants and young children. The incidence rate varies among different populations. However, genetic differences in HB patients with different epidemiological and ancestral backgrounds have not been found. In this study, we aim to analyze data from 16 patients treated at our center and collected published data from whole-exome sequencing studies on HB, and to explore the genetic differences between races. Data from a total of 75 HB patients of three races (24 Asian, 37 Caucasian and 14 Hispanic) were analyzed. We identified 16 genes with recurrent somatic mutations and 7 core pathway modules. Among them, the Wnt/ß-catenin pathway had the highest mutation rate, and the mutation frequency in Caucasians and Hispanics was approximately twice as high as that in Asians. In addition, this study compared the characteristics of gene mutations between patients who underwent preoperative chemotherapy and those who did not and found that there was no significant difference in gene mutations between the two groups. We also preliminarily verified the function of cancer-associated candidate genes (CTNNB1 and KMT2D). In conclusion, we found ethnic differences in HB biology at the genomic level, which expands our understanding of the genetics of HB in children.

Analysis of survival rates and prognosis of hepatoblastoma in children: a retrospective study from a single center in China.

Hepatoblastoma (HB) is the most common liver cancer in children, this study aims at analyzing the prognostic factors affecting the survival rates and summarizing the treatment experience. In this study, we reviewed patients with primary HB under the age of 14 years who underwent complete tumor resection from June 1997 to March 2019. The data of 72 patients were collected. Survival analysis was performed by Kaplan-Meier, multivariate Cox proportional hazards regression and linear mixed model for repeated measures (LMMRM). The 5-year and the 10-year event-free survival (EFS) of all patients were 78.2% and 73%, respectively. Both the 5-year and 10-year overall survival (OS) were 85.7%. Kaplan-Meier survival analysis showed that patients with tumor capsule infiltration (TCI) and patients with surgical margin less than 1 cm may also have a good prognosis. The Cox proportional hazards regression model analysis results were similar to the Kaplan-Meier analysis results. LMMRM analysis showed that there were significant differences in platelet, alpha-fetoprotein, C-reactive protein and hemoglobin values after surgery in the metastasis group (P < 0.05). This study suggests that patients with TCI or narrow surgical margin (<1 cm) may also have a good prognosis, and the risk stratification of HB can be used as the latest grading standard to evaluate the prognosis of patients.

Standard Liver Volume-Predicting Formulae Derived From Normal Liver Volume in Children Under 18 Years of Age.

Background: Standard liver volume (SLV) is important in risk assessment for major hepatectomy. We aimed to investigate the growth patterns of normal liver volume with age and body weight (BW) and summarize formulae for calculating SLV in children. Methods: Overall, 792 Chinese children (<18 years of age) with normal liver were enrolled. Liver volumes were measured using computed tomography. Correlations between liver volume and BW, body height (BH), and body surface area (BSA) were analyzed. New SLV formulae were selected from different regression models; they were assessed by multicentral validations and were compared. Results: The growth patterns of liver volume with age (1 day-18 years) and BW (2-78 kg) were summarized. The volume grows from a median of 139 ml (111.5-153.6 in newborn) to 1180.5 ml (1043-1303.1 at 16-18 years). Liver volume was significantly correlated with BW (r = 0.95, P < 0.001), BH (r = 0.92, P < 0.001), and BSA (r = 0.96, P < 0.001). The effect of sex on liver volume increases with BW, and BW of 20 kg was identified as the optimal cutoff value. The recommended SLV formulae were BW≤20 kg: SLV = 707.12 × BSA 1.09; BW>20 kg, males: SLV = 691.90 × BSA 1.06; females: SLV = 663.19 × BSA 1.04. Conclusions: We summarized the growth patterns of liver volume and provided formulae predicting SLV in Chinese children, which is useful in assessing the safety of major hepatectomies.

MYCN­amplified neuroblastoma cell­derived exosomal miR­17­5p promotes proliferation and migration of non­MYCN amplified cells.

Neuroblastoma (NB) is considered a highly prevalent extracranial solid tumor in young children, and the upregulation of N­myc proto­oncogene (MYCN) is closely associated with the late stages of NB and poor prognostic outcomes. The current study was designed to evaluate the effects of exosomal microRNA (miRNA/miR)­17­5p from MYCN­amplified NB cells on the proliferative and migratory potential of non­MYCN amplified NB cells. miR­17­5p was found to activate the PI3K/Akt signaling cascade by targeting PTEN, and the overexpression of miR­17­5p was found to promote cellular migration and proliferation in vitro. Further experimentation revealed that the elevated expression of miR­17­5p in SK­N­BE(2) cell­derived exosomes significantly promoted the proliferative and migratory capacities of SH­SY5Y cells by inhibiting PTEN. Collectively, these findings demonstrated that miR­17­5p derived from MYCN­amplified NB cell exosomes promoted the migration and proliferation of non­MYCN amplified cells, highlighting an exosome­associated malignant role for miR­17­5p.

Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/ß-Catenin Axis.

INTRODUCTION: Osteosarcoma is a malignant primary bone tumor. Bone marrow-derived mesenchymal stem cells-derived extracellular vesicles (BMSC-EVs) bear repair function for bone and cartilage. This study investigated the mechanism of BMSC-EVs in osteosarcoma cell proliferation, migration and invasion. METHODS: BMSC-EVs were isolated and identified. The effects of different concentrations of EVs on osteosarcoma cell proliferation, migration and invasion were evaluated. LncRNA MALAT1 expression in osteosarcoma cells was detected. BMSCs were transfected with si-MALAT1 or si-NC. The binding relationships between MALAT1 and miR-143, and miR-143 and NRSN2 were verified. Levels of NRSN2 and Wnt/ß-catenin pathway key proteins were detected. miR-143 mimic was transfected into EVs-treated osteosarcoma cells. Nude mice were injected with MG63 cells to verify the effect of EVs on osteosarcoma growth in vivo. RESULTS: BMSC-EVs facilitated proliferation, invasion and migration of osteosarcoma cells. BMSC-EVs carried MALAT1 into osteosarcoma cells. BMSC-EVs-treated osteosarcoma cells showed increased MALAT1 and NRSN2 expressions, decreased miR-143 expression, and activated Wnt/ß-catenin pathway. miR-143 mimic or si-MALAT1 reversed the effects of BMSC-EVs on osteosarcoma cells. In vivo experiment confirmed that BMSC-EVs promoted tumor growth in nude mice. DISCUSSION: BMSC-EVs promoted proliferation, invasion and migration of osteosarcoma cells via the MALAT1/miR-143/NRSN2/Wnt/ß-catenin axis. This study might offer new insights into osteosarcoma management.