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Despite recent advances in understanding the biological behavior of osteosarcoma (OS), OS is still the most common primary bone sarcoma that endangers the health of children and adolescents. High-temperature requirement A (HTRA) protease family plays an important regulatory role in numerous malignancies and acts as a prognostic biomarker. However, the function and underlying mechanisms of the HTRA family in OS development remain unknown. Through analyzing the GSE126209 dataset obtained from different Gene Expression Omnibus (GEO) databases, we found that HTRA3 as a member of the HTRA family was downregulated in OS tissues compared with that in normal tissues. Functional experiments indicated that HTRA3 overexpression suppressed malignant behaviors of OS cells in vitro and tumor growth in vivo. Mechanistically, we found that HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. Further investigation showed that XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN) and that HTRA3 caused the blockage of PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathway, characterized as the reverse of cell function caused by HTRA3 overexpression after PTEN inhibitor BpV (HOpic) treatment. Detailed investigations showed that forkhead box protein 1 (FOXP1), an oncogene in OS progression, downregulated HTRA3 expression and inhibited the transcriptional activity of HTRA3 , suggesting that HTRA3 was regulated negatively by FOXP1. In conclusion, our study demonstrates that HTRA3 is a repressor involved in OS development via the PTEN/PI3K/AKT pathway under the modulation of transcription factor FOXP1, and it may provide a therapeutic direction for OS patients. [Display omitted] • High-temperature requirement A3 (HTRA3), was screened as the candidate oncogene by the bioinformatic analysis. • HTRA3 was downregulated in osteosarcoma (OS) tissues and cells. • HTRA3 overexpression induced cell apoptosis and inhibited cell migration and invasion. • HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. • XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN). • HTRA3 suppressed the PTEN/PI3K/AKT pathway, a crucial signaling pathway contributed to the OS tumorigenesis. • Transcription factor FOXP1 was confirmed to impede the activity of HTRA3 promoter. [ABSTRACT FROM AUTHOR]

Abstract: Syncytin is a placenta-specific protein and generally believed to play a pivotal role in syncytiotrophoblast morphogenesis. In this study, transcripts of this gene were quantified by real-time RT-PCR and the translated products were measured by an indirect immunofluorescence assay. Results showed that syncytin was found to be expressed in all nine leukemia and lymphoma cell lines studied albeit at different levels and in 43 peripheral blood samples of 57 leukemia or lymphoma patients. Neither the transcripts nor the translated syncytin was detected in blood samples of normal individuals. In conclusion, peripheral blood syncytin may serve as a marker for leukemia and lymphoma. [ABSTRACT FROM AUTHOR]

With the exaggerated growth of solid tumor, the depletion of O 2 in interior cells far exceeds their blood supply, leading to low levels of O 2 in tumor microenvironment (Hypoxia). Low concentration of O 2 often cause many problems in tumor cells, including poor prognosis, increased metastasis and pro-survival changes in gene expression. Thus, developing new imaging strategy for living cells under hypoxic conditions is strongly desirable. In this review, we discuss recent progress in hypoxia-responsive fluorescent nanoprobes for imaging and cancer therapy. First, we describe two basic elements of fluorescent nanoprobes, including recognition moiety and nanomaterial-based carrier. Then, recent progress in fluorescent nanoprobes for imaging under hypoxic conditions is summarized. Finally, we outline development of hypoxia-responsive fluorescent nanoprobes for simultaneous imaging and cancer treatment. We aim to provide a comprehensive summary of application for distinguishing tumor hypoxic status, diagnosing disease and developing hypoxia-responsive anticancer nanodrugs. Image 1 • The importance of hypoxia-responsive imaging and therapy has been highlighted. • Two basic elements for fabrication of hypoxia-responsive nanoprobe are recognition moiety and nanomaterial-based carrier. • Mechanisms of moieties response to hypoxia are explained, and characteristics of fluorescent nanoprobes are presented. • We focus on recent progress in hypoxia-responsive fluorescent nanoprobes for imaging and cancer therapy. [ABSTRACT FROM AUTHOR]