ABSTRACT
Ephrin receptor A7 (EphA7) is a member of the Eph receptor family. It is widely involved in signal transduction between cells, regulates cell proliferation and differentiation, and participates in developing neural tubes and brain. In addition, EphA7 also has a dual role of tumor promoter and tumor suppressor. It can participate in cell proliferation, migration and apoptosis through various mechanisms, and affect tumor differentiation, staging and prognosis. EphA7 may be a potential diagnostic marker and tumor treatment target. This article reviews the effects of EphA7 on a variety of tumor biological processes and pathological characteristics, as well as specific effects and regulatory mechanisms.
Subject(s)
Neoplasms , Receptor, EphA7 , Apoptosis , Cell Proliferation , Genes, Tumor Suppressor , Humans , Neoplasms/genetics , Receptor, EphA7/genetics , Receptor, EphA7/metabolism , Signal Transduction/physiologyABSTRACT
Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.
Subject(s)
Bone Neoplasms , MicroRNAs/metabolism , Osteosarcoma , RNA, Long Noncoding/genetics , Receptor, EphA7/metabolism , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness , Osteosarcoma/genetics , Osteosarcoma/pathologyABSTRACT
Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.
Subject(s)
Humans , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Osteosarcoma/genetics , Osteosarcoma/pathology , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Down-Regulation , Gene Expression Regulation, Neoplastic , Cell Movement , Receptor, EphA7/metabolism , Cell Line, Tumor , Cell Proliferation , Neoplasm InvasivenessABSTRACT
Functional impairment after spinal cord injury (SCI) is partially attributed to neuronal cell death, with further degeneration caused by the accompanying apoptosis of myelin-forming oligodendrocytes. The Eph receptor protein tyrosine kinase family and its cognate ligands, the ephrins, have been identified to be involved in axonal outgrowth, synapse formation, and target recognition, mainly mediated by repulsive activity. Recent reports suggest that ephrin/Eph signaling might also play a role as a physiological trigger for apoptosis during embryonic development. Here, we investigated the expression profile of EphA7, after SCI, by using a combination of quantitative real-time PCR (QRT-PCR) and immunohistochemical techniques. QRT-PCR analysis showed an increase in the expression of full-length EphA7 at 7 days postinjury (DPI). Receptor immunoreactivity was shown mostly in astrocytes of the white matter at the injury epicenter. In control animals, EphA7 expression was observed predominantly in motor neurons of the ventral gray matter, although some immunoreactivity was seen in white matter. Furthermore, blocking the expression of EphA7 after SCI using antisense oligonucleotides resulted in significant acceleration of hindlimb locomotor recovery at 1 week. This was a transient effect; by 2 weeks postinjury, treated animals were not different from controls. Antisense treatment also produced a return of nerve conduction, with shorter latencies than in control treated animals after transcranial magnetic stimulation. We identified EphA7 receptors as putative regulators of apoptosis in the acute phase after SCI. These results suggest a functional role for EphA7 receptors in the early stages of SCI pathophysiology.