ROS-responsive thermosensitive polypeptide hydrogels for localized drug delivery and improved tumor chemoimmunotherapy.

In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogel demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogel effectively inhibited tumor growth, prolonged animal survival time and promoted anti-tumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogel exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective anti-tumor treatment and suppression of tumor recurrence.

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.

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.

Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes.

BACKGROUND: The role of ferroptosis in tumorigenesis has been confirmed in previous studies. However, the comprehensive analysis of ferroptosis-related gene (FRG) to study the role of FRG in soft tissue sarcoma (STS) is lacking. METHODS: RNA sequencing profile of TCGA-SARC cohort and GTEx were used to select differentially expressed FRGs (DEFRGs). Univariate, LASSO, and multivariate Cox analyses were selected to determine overall survival (OS)- and disease-free survival (PFS)-related FRGs. Two prognostic signatures were established and validated in two independent sets from Gene Expression Omnibus (GEO). Finally, the expression of key FRGs were validated with RT-qPCR. RESULTS: In total, 198 FRGs (90.4%) were abnormally expressed in STS. Twelve DEFRGs were incorporated in the final signatures and showed favorable discrimination in both training and validation cohorts. Patients in the different risk groups not only showed different prognosis, but also showed different infiltration of immune cells. Two nomograms combining signature and clinical variables were established and the C-indexes were 0.852 and 0.752 for the OS and DFS nomograms, respectively. Finally, the expression of NOX5, HELLS, and RPL8 were validated with RT-qPCR. CONCLUSION: This comprehensive analysis of the FRG landscape in STS revealed novel FRGs related to carcinogenesis and prognosis. These findings have implications for prognosis and therapeutic responses, which revealed potential prognostic biomarkers and promote precision medicine.

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.

[A comprehensive analysis of potential prognostic biomarkers for MYCN-amplified neuroblastoma].

OBJECTIVE: To study the differentially expressed mRNAs between MYCN-amplified neuroblastoma (NB) and non-amplified NB, to screen out the genes which can be used to predict the prognosis of MYCN-amplified NB, and to analyze their value in predicting prognosis. METHODS: NB transcriptome data and the clinical data of children were obtained from the TARGET database. According to the presence or absence of MYCN amplification, the children were divided into two groups: MYCN amplification (n=33) and non-MYCN amplification (n=121). The expression of mRNAs was compared between the two groups to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis was performed to investigate the main functions of DEGs. The Cox proportional-hazards regression model analysis was used to investigate the genes influencing the prognosis of MYCN-amplified NB. The children were divided into a high-risk group (n=77) and a low-risk group (n=77) based on the median of risk score. A survival analysis was used to compare survival rate between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of risk score in predicting the prognosis of children with MYCN-amplified NB. RESULTS: A total of 582 DEGs were screened out, and they were involved in important biological functions such as ribosome composition, expression of cell adhesion molecules, and activity of membrane receptor protein. The multivariate Cox regression model analysis showed that FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes had a marked influence on the prognosis of the children with NB in the MYCN amplification group (P<0.05). The survival analysis showed that the high-risk group had a significantly lower overall survival rate than the low-risk group (P<0.05). The ROC curve analysis showed that risk score had a certain value in predicting the prognosis of the children with NB in the MYCN amplification group (P<0.05), with an area under the ROC curve of 0.729, an optimal cut-off value of 1.316, a sensitivity of 53.2%, and a specificity of 84.4%. CONCLUSIONS: The mRNA expression of FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes can be used as biomarkers to predict the prognosis of MYCN-amplified NB, which can help to refine clinical risk stratification.

LncRNA cancer susceptibility candidate (CASC7) upregulates phosphatase and tensin homolog by downregulating miR-10a to inhibit neuroblastoma cell proliferation.

Long non-coding (lncRNA) cancer susceptibility candidate (CASC7) plays a tumor-suppressive role in several malignancies. In this study, the role of CASC7 in neuroblastoma was investigated for the first time. We observed the downregulation of CASC7 in neuroblastoma tissues compared to non-cancer tissues of neuroblastoma patients. Across neuroblastoma tissues, CASC7 was inversely correlated with microRNA-10a (miR-10a) but positively correlated with phosphatase and tensin homolog mRNA. In neuroblastoma cells, CASC7 overexpression led to downregulated miR-10a but upregulated phosphatase and tensin homolog. Furthermore, miR-10a overexpression led to downregulated phosphatase and tensin homolog and reduced effects of CASC7 overexpression. CASC7 overexpression resulted in inhibition, while miR-10a overexpression resulted in increased proliferation rate of neuroblastoma cells. We therefore concluded that lncRNA CASC7 may upregulate phosphatase and tensin homolog by downregulating miR-10a to inhibit neuroblastoma cell proliferation.

MicroRNA-429 inhibits neuroblastoma cell proliferation, migration and invasion via the NF-κB pathway.

BACKGROUND: MicroRNAs (miRNAs or miRs) can participate in the development and progression of neuroblastoma. Many studies have indicated that miR-429 can participate in tumor development. However, the mechanism underlying miR-429-mediated progression of neuroblastoma remains largely unclear. METHODS: Colony formation and apoptosis assays were used to determine the effect of miR-429 on cell proliferation. Its impact on cell migration was determined using the wound-healing and Transwell assays. The target gene of miR-429 was confirmed via western blotting and luciferase reporter assays. A nude mouse xenograft model with miR-429 overexpression was used to assess the effect on tumor growth. RESULTS: Our findings indicate that miR-429 is downregulated in neuroblastoma cell lines. We also found that it can induce apoptosis and inhibit proliferation in cells of those lines. MiR-429 can bind to the 3'-UTR of IKKß mRNA and overexpression of IKKß can reverse cell proliferation, blocking the effect of miR-429. Furthermore, miR-429 overexpression inhibited neuroblastoma growth in our nude mouse xenograft model. CONCLUSION: We provide important insight into miR-429 as a tumor suppressor through interaction with IKKß, which is a catalytic subunit of the IKK complex that activates NF-κB nuclear transport. Our results demonstrate that miR-429 may be a new target for the treatment of neuroblastoma.

Toxoplasma gondii infection in children with lymphoma in Eastern China: seroprevalence, risk factors and case-control studies.

Epidemiological data for Toxoplasma gondii regarding malignancy have gained increasing attention; however, the information about T. gondii infection among children with malignant lymphoma (ML) in China is unclear. Therefore, 314 children with lymphoma and 314 healthy children, age- and gender-matched, were recruited to estimate the seroprevalence of T. gondii in the participants and identify the risk factors of infection. Blood samples from all participants were collected and examined for T. gondii IgG and IgM antibodies using ELISA. The results showed that the overall seroprevalence of T. gondii antibodies (including IgG and/or IgM) in ML patients and healthy controls was 19.8% and 9.9%, respectively. Contact with the cats, consumption of oysters and history of chemotherapy were estimated to be the risk factors for T. gondii infection in children with lymphoma by multivariable logistic regression analysis, whereas in healthy children, contact with cats and consumption of oysters were the risk factors. Moreover, among various histological types of lymphoma, individuals with NK/T-cell lymphoma, B-small lymphocytic lymphoma, marginal zone B-lymphoma and Hodgkin's lymphoma had a higher seroprevalence than healthy controls (P < 0.05). These findings indicated the high prevalence of T. gondii infection in children with lymphoma, and hence, efforts should be performed to evaluate the effect of the infection further in lymphoma patients.

Role of SNHG7-miR-653-5p-STAT2 feedback loop in regulating neuroblastoma progression.

Long noncoding RNAs (lncRNAs) are reported to be involved in the pathology of numerous cancers, including neuroblastoma (NB). lncRNA SNHG7 has been recognized as a carcinogen in several cancers, but its role in NB progression remains unknown. Our study revealed that SNHG7 expression was markedly higher in NB tissues than that in nontumor tissues. Besides, upregulated SNHG7 was greatly correlated with poor overall survival of NB patients. Functionally, the loss-of-function assays demonstrated that knockdown of SNHG7 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition in NB cells. Mechanically, the bioinformatics analysis predicted that miR-653-5p was the shared partner of SNHG7 and signal transducer and activator of transcription 2 (STAT2). Unsurprisingly, we further confirmed that SNHG7 could interact with miR-653-5p and therefore functioned as the ceRNA of STAT2 so as to regulate STAT2 expression in NB cells. Moreover, STAT2 expression was in inverse proportion to miR-653-5p level but in positive proportion to SNHG7 level in NB tissues. Importantly, the repressed NB progression induced by silenced SNHG7 was reversed by STAT2 overexpression or miR-653-5p inhibitors. Jointly, our findings elucidated SNHG7 facilitated NB progression through the miR-653-5p/STAT2 pathway, providing a novel therapeutic target and prognostic biomarker for this disease.

Diagnosis of 65 cases of ampullary renal pelvis after postnatal follow-up of 1,167 newborn infants with prenatally suspected hydronephrosis.

The aim of the present study was to assess the morbidity of ampullary renal pelvis (ARP) and document its natural history in post-natal life. A total of 1,167 newborn infants with prenatally suspected hydronephrosis were retrospectively analyzed. Of these, 65 patients were diagnosed with ARP by computed tomography urography (CTU) and/or magnetic resonance urography (MRU). All cases were followed up with ultrasonogrophy at 1, 3, 6 and 12 months after birth, and one case was followed up for 5 years. Changes in the separation of the renal pelvis collection system were recorded. Children with ARP accounted for 5.57% of the total cases (65/1,167) followed-up. No lack of connection between the renal calyces and the renal pelvis was detected. The long-term follow-up revealed that the separation of the renal pelvis collection system did not tend to increase over time. In addition to imaging examinations, long-term follow-up observation is recommended for the accurate diagnosis of pediatric ARP, particularly for differentiation from hydronephrosis.