EBF1-mediated up-regulation of lncRNA FGD5-AS1 facilitates osteosarcoma progression by regulating miR-124-3p/G3BP2 axis as a ceRNA

Background As a skeletal malignancy, osteosarcoma has high incidence among primary malignant bone tumors. With increasing researches on molecules which mediate cancer progression, molecular mechanism has gradually become the pivot of osteosarcoma research and treatment. Aim Our study aimed at investigating the function of G3BP stress granule assembly factor 2 (G3BP2), which is an oncogene for breast cancer (BC) and prostate cancer but remains unknown in osteosarcoma cells. Methods Related gene expression was confirmed by RT-qPCR. Functional assays including immunofluorescence (IF), colony formation, transferase-mediated dUTP nick-end labeling (TUNEL) as well as transwell assays were utilized to test the cell biological process caused by the genes. Meanwhile, RNA pull-down assay, along with luciferase reporter and RNA immunoprecipitation (RIP) assays, was utilized to detect the interaction G3BP2, miR-124-3p and FGD5 antisense RNA 1 (FGD5-AS1) may exert on the regulation of osteosarcoma cells. Results G3BP2 was with high expression in osteosarcoma cells, and it aggravated the malignant cell behaviors in osteosarcoma. Additionally, miR-124-3p was verified to negatively regulate G3BP2 expression in osteosarcoma cells. Moreover, lncRNA FGD5-AS1 was predicted and testified to be the sponge of miR-124-3p and modulated G3BP2 expression positively. Subsequently, FGA5-AS1 accelerated osteosarcoma cell proliferation through up-regulating G3BP2. Furthermore, we identified EBF transcription factor 1 (EBF1) as the transcription factor for FGA5-AS1, and EBF1 served as a tumor facilitator in osteosarcoma cells. Conclusion EBF1 induced-FGA5-AS1 aggravated osteosarcoma cell malignancy by targeting miR-124-3p and G3BP2.

Automated summary

In this study, we found that G3BP2 is highly expressed in osteosarcoma cells and exacerbates their malignant behavior. MiR-124-3p was shown to negatively regulate the expression of G3BP2 in osteosarcoma cells. FGD5-AS1 was identified as a sponge for miR-124-3p and positively modulated G3BP2 expression. FGA5-AS1 promotes osteosarcoma cell proliferation by upregulating G3BP2. EBF1 was identified as the transcription factor for FGA5-AS1 and serves as a tumor facilitator in osteosarcoma cells.