ABSTRACT
Osteosarcoma is a highly mortal bone tumor, with a high metastatic potential, promoted in part by the enzyme procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2). Increasing level of PLOD2 in osteosarcoma tissue correlates with lymphatic and distant metastasis. The adipokine apelin (APLN) is also found in different cancers and APLN upregulation promotes angiogenesis and metastasis, but its effects on osteosarcoma metastasis are uncertain. We explored APLN functioning in metastatic osteosarcoma. An analysis of records from the Gene Expression Omnibus (GEO) database showed higher levels of APLN expression in osteosarcoma tissue than in normal tissue. Similarly, levels of APLN and PLOD2 mRNA synthesis were upregulated in osteosarcoma tissue. Levels of APLN and PLOD2 protein correlated positively with osteosarcoma clinical stages. APLN increased PLOD2 expression in human osteosarcoma cell lines and cell migration via the mammalian Sterile 20-like kinase 1 (MST1), monopolar spindle-one-binder protein (MOB)1, and YAP cascades, and through hsa_circ_0000004 functioning as a sponge of miR-1303. We also found that knockdown of APLN antagonized lung metastasis in mice with osteosarcoma. APLN may be a therapeutic target in osteosarcoma metastasis.
Subject(s)
Apelin , Bone Neoplasms , Hippo Signaling Pathway , MicroRNAs , Osteosarcoma , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase , RNA, Circular , Animals , Humans , Mice , Apelin/genetics , Apelin/metabolism , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , Osteosarcoma/genetics , Osteosarcoma/pathology , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism , RNA, Circular/metabolismABSTRACT
Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.
Subject(s)
Adipokines , Apelin , MicroRNAs , Prostatic Neoplasms , Animals , Humans , Male , Mice , Adipokines/genetics , Adipokines/physiology , Apelin/genetics , Apelin/physiology , Cell Line, Tumor , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Tissue Inhibitor of Metalloproteinase-2/genetics , Cell Movement , Neoplasm MetastasisABSTRACT
BACKGROUND: In high income countries in Europe and North America, early identification and intervention for autism spectrum disorders (ASD) have been linked to improved long-term outcomes. However, in most low and middle income countries (LMIC) little is known about use or availability of such services, which limits the ability of policy and development planning. The purpose of the present study was assess the use of ASD services in Vietnam, an Asian LMIC, in order to identify areas within the field that should be specifically targeted to improve ASD services in Vietnam. METHODS: Surveys were conducted in six different cities across Vietnam with 90 parents/caregivers of children with ASD, 115 professionals working with children with ASD, and 10 directors of agencies providing ASD services. Parents/caregivers' survey assessed demographics and information regarding their child's symptoms and services the child received. Professionals' survey assessed their demographic and professional background, the ASD services they provide, and their perspective on the quality of ASD services at their agency. Directors' survey included these same questions as well as additional questions regarding the operation of the agency. RESULTS: Early identification and intervention ASD services are available in Vietnam, at least in major cities. However, there is a lack of well-trained professionals, the tools used for evaluation and diagnosis are limited, outdated and unstandardized, and the quality of services is questionable. Most importantly, a scientific evidence base for services is absent, and the country lacks an official governmental policy for supporting children with ASD. CONCLUSIONS: Research directly assessing the quality of ASD services in Vietnam is needed. Most centrally, efforts at facilitating governmental policy and support advocacy are needed to increase the likelihood that families and children with ASD will receive appropriate and effective services.