No abstract

Various studies demonstrated that bone morphogenetic proteins (BMPs) and their antagonists contribute to the development of cancers. Chordin‐like 2 (CHRDL2) is a member of BMP antagonists. However, the role and its relative mechanism of CHRDL2 in osteosarcoma remains unclear. In the present study, we demonstrated that the expression of CHRDL2 was significantly upregulated in osteosarcoma tissues and cell lines compared with adjacent tissues and human normal osteoblast. Inhibition of CHRDL2 decreased the proliferation and colony formation of osteosarcoma cells in vitro, as well as the migration and invasion. CHRDL2 overexpression induced the opposite effects. CHRDL2 can bind with BMP‐9, thus decreasing BMP‐9 expression and the combination to its receptor protein kinase ALK1. It was predicted that BMP‐9 regulates PI3K/AKT pathways using gene set enrichment analysis. Inhibition of CHRDL2 decreased the activation of PI3K/AKT pathway, while overexpression of CHRDL2 upregulated the activation. Increasing the expression of BMP‐9 reversed the effects of CHRDL2 overexpression on the activation of PI3K/AKT pathway, as well as the proliferation and metastasis of osteosarcoma cells. Take together, our present study revealed that CHRDL2 upregulated in osteosarcoma tissues and cell lines, and promoted osteosarcoma cell proliferation and metastasis through the BMP‐9/PI3K/AKT pathway. CHRDL2 maybe an oncogene in osteosarcoma, as well as novel biomarker for the diagnosis of osteosarcoma.

Dysregulation of immune cell infiltration in the tumor microenvironment contributes to the progression of osteosarcoma (OS). In the present study, we explored genes related to immune cell infiltration and constructed a risk model to predict the prognosis of and guide therapeutic strategies for OS. The gene expression profile of OS was obtained from TARGET and Gene Expression Omnibus, which were set as the discovery and verification cohorts. CIBERSORT and Kaplan survival analyses were used to analyze the effects of immune cells on the overall survival rates of OS in the discovery cohort. Differentially expressed gene (DEG) analysis and protein–protein interaction (PPI) networks were used to analyze genes associated with immune cell infiltration. Cox regression analysis was used to select key genes to construct a risk model that classified OS tissues into high- and low-risk groups. The prognostic value of the risk model for survival and metastasis was analyzed by Kaplan–Meier survival analyses, receiver operating characteristic curves, and immunohistochemical experiments. Immunological characteristics and response effects of immune checkpoint blockade (ICB) therapy in OS tissues were analyzed using the ESTIMATE and Tumor Immune Dysfunction and Exclusion algorithms, while sensitivity for both targeted and chemotherapy drugs was analyzed using the OncoPredict algorithm. It was demonstrated that the high infiltration of resting dendritic cells in OS tissues was associated with poor prognosis. A total of 225 DEGs were found between the high- and low-infiltration groups of OS tissues, while 94 genes interacted with others. Through COX analyses, among these 94 genes, four genes (including AOC3, CDK6, COL22A1, and RNASE6) were used to construct a risk model. This risk model showed a remarkable prognostic value for survival rates and metastasis in both the discovery and verification cohorts. Even though a high microsatellite instability score was observed in the high-risk group, the ICB response in the high-risk group was poor. Furthermore, using OncoPredict, we found that the high-risk group OS tissues were resistant to seven drugs and sensitive to 25 drugs. Therefore, our study indicates that the resting dendritic cell signature constructed by AOC3, CDK6, COL22A1, and RNASE6 may contribute to predicting osteosarcoma prognosis and thus therapy guidance.

Infants aged 3 months or younger may suffer from intussusception and most of them present with typical symptoms. Early diagnosis and treatment are needed for a good prognosis. Intrauterine intussusception may be an etiological factor for ileal atresia.

Osteosarcoma is a common type of bone tumor that primarily occurs in children and young adults. MicroRNA (miRNA/miR) dysregulation is associated with the progression of osteosarcoma; therefore, the aim of the present study was to investigate the biological functions and molecular mechanisms of miR-145-5p in osteosarcoma. The expression of miR-145-5p in osteosarcoma tissues and cell lines was quantified using reverse transcription-quantitative PCR (RT-qPCR). The effect of miR-145-5p on the proliferation of osteosarcoma cells was detected using cell counting Kit-8 and colony formation assays, as well as cell cycle distribution analysis. The effect of miR-145-5p on tumor growth was further investigated in vivo using a subcutaneous tumor model in nude mice. The interaction between miR-145-5p and E2F transcription factor 3 (E2F3) was determined using bioinformatics analysis, a luciferase assay, RT-qPCR and western blotting. The results revealed that miR-145-5p expression was decreased in osteosarcoma cell lines and tissues compared with the corresponding normal controls. Increased miR-145-5p expression inhibited the proliferation and colony formation ability of osteosarcoma cells, and induced G 1 phase arrest. Furthermore, mice injected with tumor cells overexpressing miR-145-5p exhibited smaller tumors than those in the control group. Further investigation revealed that miR-145-5p binds to and decreases the expression of E2F3. In addition, the mRNA levels of E2F3 were negatively associated with miR-145-5p in osteosarcoma tissues, and increasing E2F3 expression abrogated the inhibitory effects of miR-145-5p on osteosarcoma cells. collectively, the results obtained in the present study suggest that miR-145-5p may suppress the progression of osteosarcoma, and may serve as a useful biomarker for the diagnosis of osteosarcoma, as well as a therapeutic target.