NAIF1 suppresses osteosarcoma progression and is regulated by miR‐128

Abstract

Nuclear apoptosis‐inducing factor 1 (NAIF1) acts as an oncogene and involves in tumorigenesis in several cancers. However, the expression and mechanism of NAIF1 in osteosarcoma remains unclear. In this study, we demonstrated the downregulation of NAIF1 expression in both osteosarcoma tissues and cell lines. We next explored the potential role of NAIF1 in osteosarcoma cell proliferation and migration. The result showed that overexpression of NAIF1 evidently suppressed the cell proliferation and invasion of osteosarcoma. Furthermore, we investigated the potential mechanisms accounting for dysregulation of NAIF1 in osteosarcoma. The bioinformatic prediction and luciferase reporter assay revealed that miR‐128 is a direct upstream regulator of NAIF1 and regulates NAIF1 expression by binding the 3′‐UTR of NAIF1. Consistent with previous study, we found that miR‐128 was upregulated in both osteosarcoma tissues and cell lines. Moreover, miR‐128 expression levels were inversely correlated with that of NAIF1 in osteosarcoma tissues. Finally, functional assay showed that miR‐128 significantly suppressed osteosarcoma progression partially mediated by inhibiting NAIF1 expression. These data indicate that the miR‐128 and its target gene NAIF1 played important roles by regulating OS cell proliferation and migration phenotype. Significance of the study Osteosarcoma (OS) is the most common malignant bone tumour and the second leading cause of cancer‐related death affecting children and adolescents. Nuclear apoptosis‐inducing factor 1 (NAIF1) plays an inhibitory role in the initial steps of different carcinomas. However, the expression and mechanism of NAIF1 in osteosarcoma remains unclear. The data of this study indicated that the miR‐128 and its target gene NAIF1 played important roles by regulating OS cell proliferation and migration phenotype. It was demonstrated that NAIF1 would demonstrate important regulative effects and may be a promising therapeutic target of OS.

miRNA-128 modulates bone neoplasms cells proliferation and migration through the WNT/β-catenin and EMT signal pathways

“…miRNAs are involved in the diagnosis of OA as well as in its treatment [ 29 , 30 ]. The data in a previous study indicated that the miR-128 downregulation inhibits osteosarcoma cell proliferation and migration phenotype [ 31 ]. Activation of Wnt/β-catenin signaling pathways play essential roles and may rescue chemotherapy drug resistance by targeting Beclin 1 in osteosarcoma cells [ 32 ].…”

The Proteomic Expression of Nuclear Apoptosis-Inducing Factor1 (NAIF1) in Colorectal Tissues

“…Several studies have described the proteomic expression of NAIF1 gene [10][11][12][13][14] . Our results are consistent with the previous studies were done on NAIF1 gene expression showed that, NAIF1 is expressed in both cancer tissue or cancer cell lines and in non-cancerous or normal tissue [10,12] , this expression was strong or high in non-cancerous or normal tissue compared with weak or little seen in cancerous one.…”

“…The human gene encoding nuclear apoptosis inducing factor 1 (NAIF1) is located on chromosome 9q34.11, and reported to repress the progression of several human cancers [9,[10][11][12][13][14] .…”

“…In gastric cancer [10,12] , prostate carcinoma [11] , in osteosarcoma cells [13] , in non-small-cell lung cancer [14] . NAIF1 inhibit the progression of cancer by inducing apoptosis and it plays an important role in control of the expression of some pivotal anti-cancer or apoptosisrelated genes in physiological level [10,12] .…”

“…NAIF1 inhibit the progression of cancer by inducing apoptosis and it plays an important role in control of the expression of some pivotal anti-cancer or apoptosisrelated genes in physiological level [10,12] . These findings may indicate that it is very likely that NAIF1 may predominantly act as a tumor-suppressive gene, possibly through the activation of apoptotic pathways, in various types of cancers [10][11][12][13][14] . In the present study the model retained for the study of the expression of NAIF1 neogenic protein by the western blot method was an in vitro model of human colorectal cancerous and non-cancerous tissues, using the protein extracted from these tissues and by the antibodies synthesized by Arnaoty et al [15] , that allow the study of the expression and the analysis of neogenic recombinase corresponding to NAIF1 protein.…”