| Glioma is the most common primary intracranial tumor.At present,medical treatment of glioma mainly relies on surgical resection adjuvant radiotherapy and chemotherapy,but its therapeutic and prognostic effects are not ideal.Therefore,exploring the mechanism underlying the genesis and progession of gliomas to find the new molecular targets with therapeutic potential is currently the hotspots of glioma research.PDLIM4 is an actin binding protein,which plays a very important role in cytoskeleton growth and exercise.PDLIM4 was initially identified as a candidate tumor suppressor gene,and some studies have also proved that it has the function of inhibiting tumor growth in prostate cancer,thyroid cancer,renal cell carcinoma and ovarian cancer.At present,how PDLIM4 regulates the growth of gliomas and the detailed molecular mechanisms involved are still unclear.Here,we have identified PDLIM4 protein whose expression level is closely related to the poor prognosis of gliomas through bioinformatics analysis.Tests on tissue samples from patients with glioma showed the mRNA and protein levels of PDLIM4 were significantly higher in glioblastoma,compared with low-grade glioma.Then overexpression and knockdown of PDLIM4 in the glioma U87 cell line were used to test the effects of PDLIM4 in the proliferation and invasion of glioma cells via CCK8 and Transwell experiments.It was found that knockdown of PDLM4 in glioma cells can significantly inhibit cell growth,proliferation and invasion,but overexpression of PDLIM4 does not affect the phenotypes of glioma cells.Mechanism studies revealed that knocking down PDLIM4 could activate Caspase 3 and Caspase 8 leading to cellular apoptosis and increase the level of autophagy.Furthermore,knocking down PDLIM4 could affect the assembly of tumor cytoskeleton through actin,leading to changes in cell morphology and inhibiting tumor cell invasion and migration.We also found that the mRNA of the PDLIM4 gene in glioma samples has intron retention(Intron Retention,IR),and this intron retention fragment is related to glioblastoma.In summary,we confirmed that the expression level of PDLIM4 is positively correlated with the malignant degree of glioma,and explored its effect on the growth and invasion of glioma cells and underlying mechanisms.We speculate that PDLIM4 may be a glioma marker,and may become a potential therapeutic target for clinical treatment of glioma.The innovations of this research are as follows:(1)We explored the effects of overexpression and knockdown of PDLIM4 on the proliferation and invasion of glioma cell lines.(2)We found that knocking down PDLIM4 will activate the caspase 3 and Caspase 8 of the glioma cell line,cause cell apoptosis,and increase the level of autophagy in the cell.(3)We found that there is intron retention in PDLIM4 mRNA,and this intron retention fragment can encode protein and has a significant correlation with glioblastoma. |
