Molecular Mechanism Of NUDT21 Regulating The Proliferation Of Tongue Squamous Cell Carcinoma Cells

Oral squamous cell carcinoma（OSCC）has the characteristics of rapid growth and high metastasis rate.Its incidence rate is increasing year by year,and the overall 5-year survival rate is less than 60%.At present,there are many studies on oral squamous cell carcinoma,but the relevant mechanism of its malignant progression is still unclear.Exploring the new pathogenesis of OSCC is an urgent problem to be solved.NUDT21 is an RNA binding protein that plays an important role in the regulation of a variety of biological reactions.Studies have found that NUDT21 is closely related to many human tumors,but its relationship with OSCC has not been confirmed..Therefore,this paper aims to investigate the effect of NUDT21 on the biological behavior of tongue squamous cancer cells and explore its molecular mechanism of regulating the progression of tongue squamous cell carcinoma.To provide ideas for exploring new treatment methods of OSCC.Purpose:To study the expression of NUDT21 in tongue squamous cell carcinoma cells and the effect of down-regulation of NUDT21 on the proliferation of tongue squamous cell carcinoma cells.To explore the molecular mechanism of NUDT21 expression regulating the progression of tongue squamous cell carcinoma,so as to provide a new theoretical basis for the malignant biological mechanism of OSCC.Methods:Firstly,16 cases of tongue squamous cell carcinoma and 15 cases of adjacent tissues were stained by immunohistochemistry to analyze the staining of the two groups of samples.Then,the knockdown NUDT21 lentivirus vector was constructed and stably transfected into CAL27 and SCC-25 tongue squamous cell carcinoma cell lines.The effect of NUDT21 gene silencing on the growth state of cancer cells was observed through cell function experiment.Finally,the key genes differentially expressed after NUDT21 silencing were screened and verified by microarray experiment.Results:1.Immunohisto chemical staining showed that NUDT21 gene was highly expressed in tongue squamous cell carcinoma cells compared with paracancerous tissue cells.2.When the NUDT21 of CAL27 and SCC-25 cells was knocked down,the corresponding protein expression decreased.At the same time,the expression of NUDT21 was down-regulated,which significantly inhibited the proliferation rate of tongue squamous cell carcinoma cells in vitro.Flow cytometry showed that the decreased expression of NUDT21 in tongue squamous cell carcinoma promoted apoptosis3.Through the analysis of human genome-wide expression microarray,a total of 252 up-regulated genes and 432 down-regulated genes were screened.4.Bioinformatics analysis found that the down-regulation of NUDT21 caused changes in downstream gene expression,resulting in changes in a series of signal pathways such as adipocytokine signal pathway,NFAT pathway and insulin signal pathway.These pathways mainly involved intracellular transport,cell cycle regulation,biomacromolecule localization,protein transport,nucleotide formation and binding.5.The downstream key genes were screened for PCR and Western blot verification.The results showed that after the down-regulation of NUDT21,the expression of downstream SMC1A and PSMC2 genes were up-regulated and the expression of HNRNPA0 and TIPRL genes were down-regulated.