Novel Role of HAX-1 in Neurons Protection After Spinal Cord Injury Involvement of IRE-1.

Spinal cord injury (SCI) is one of the diseases with high probability of causing disability in human beings, and there is no reliable treatment at present. Neuronal apoptosis is a vital component of secondary injury and plays a critical role in the development of neurological dysfunction after spinal cord injury. In this study, we found that the expression and distribution of HAX-1 in neurons increased 1 day after SCI. PC12 cells overexpressing HAX-1 showed decreased apoptosis and PC12 cells are more likely to undergo apoptosis after down-regulating HAX-1, which was confirmed via TUNEL experiments. We found GRP94 showed the same trend as HAX-1 in expression and interacted with HAX-1 and IRE-1 in both spinal cord tissue and PC12 cells, and this interaction seems to be enhanced after SCI. When the expression of HAX-1 was up-regulated, GRP94 also increased, but IRE-1 did not change at all. Further studies showed that overexpression of HAX-1 decreased the expression of pIRE-1, rather than IRE-1, and downstream proteins of the IRE signaling pathway (Caspase12, pJNK and CHOP) were significantly reduced, and vice versa. In animals treated with HAX-1 expressing adenovirus there are more neuronal cells remaining in the damaged spinal cord tissue, and hindlimb motor function of rats was significantly improved. So, we speculate that HAX-1 might play a role in protecting neurons from apoptosis after SCI by regulating the IRE-1 signaling pathway via promoting the dissociation of GRP94 from IRE-1. This may provide a theoretical basis and a potential therapeutic target for clinical improvement of neural function recovery after SCI.

LncRNA NR_027471 Functions as a ceRNA for miRNA-8055 Leading to Suppression of Osteosarcoma by Regulating the Expression of TP53INP1.

Osteosarcoma is a malignancy with high aggressiveness and poor prognosis, which occurs mainly in children. The therapeutic strategy against osteosarcoma includes surgery combined with chemotherapy and radiotherapy. Although the treatment of osteosarcoma has been improved in recent years, there is a large proportion of patients with incurable osteosarcoma. Investigation of the mechanism of osteosarcoma progression would be of great help in discovering therapeutic targets for this disease. Long non-coding RNAs play critical roles in the pathogenesis of different types of cancer. The current study showed that long non-coding RNA NR_027471 was downregulated in osteosarcoma cells. In vitro and in vivo studies indicated that upregulation of NR_027471 impeded the viability, proliferation, and invasion of osteosarcoma, as well as induced cell cycle arrest at G1. In addition, binding of miR-8055 to NR_027471 was demonstrated, thereby influencing the expression of tumor protein p53 inducible nuclear protein 1 (TP53INP1). Knockdown of NR_027471 promoted epithelial-mesenchymal transition by inhibiting E-cadherin and increasing the expression of zinc finger E-box-binding homeobox 1 (ZEB1), Snail, and fibronectin. These results suggested that overexpression of NR_027471 upregulated TP53INP1 by sponging to miR-8055, leading to suppression of osteosarcoma cell proliferation and progression.

The upregulation of annexin A2 after spinal cord injury in rats may have implication for astrocyte proliferation.

Annexin A2 (ANXA2), is a member of the annexin family of proteins that exhibit Ca2+-dependent binding to phospholipids. One attractive biological function of ANXA2 is participating in DNA synthesis and cell proliferation. Previous studies have shown that ANXA2 play a role in the development of the central nervous system. However, the biological function of ANXA2 after spinal cord injury (SCI) is still with limited acquaintance. In the present study, we performed a SCI model in adult rats and investigated the dynamic changes of ANXA2 expression in the spinal cord. Western blot analysis indicated a striking expression upregulation of ANXA2 after SCI. Immunohistochemistry further confirmed that ANXA2 immunoactivity was expressed at low levels in normal condition and increased at 5day after SCI. Double immunofluorescence staining prompted that ANXA2 immunoreactivity was found in astrocytes and neurons. Interestingly, ANXA2 expression was increased predominantly in astrocytes. We also examined the expression profiles of proliferating cell nuclear antigen (PCNA), Cyclin D1 and active caspase-3 in the injured spinal cords by western blot. Co-expression of ANXA2/PCNA, ANXA2/Cyclin D1 was detected in glial fibrillary acidic protein. Importantly, double immunofluorescence staining revealed that cell proliferation evaluated by PCNA appeared in many ANXA2-expressing cells and rare caspase-3 was observed in ANXA2-expressing cells after SCI. In addition, ANXA2 knockdown in astrocytes resulted in the increase of PCNA expression after LPS stimulation, showing that ANXA2 inhibited astrocyte proliferation after inflammation. Our data suggested that ANXA2 might play important roles in CNS pathophysiology after SCI.