Regulation Of STK33 Gene In Non-small Cell Lung Cancer In The Ras-MAPK Signaling Pathway

Objective:Discussion on regulation of STK33 in Non-small cell lung cancer (NSCLC) for Ras-MAPK signaling pathways,Clearly provides a theoretical basis in the promotion of NSCLC metastasis and invasion of the mechanism, thus providing theoretical support for NSCLC targeted therapy to find new targets. Methods:With already established stable high metastatic cell L9981 of human large cell lung cancer cell L9981 and low metastatic cell NL9980 of human large cell lung cancer cell,detect mRNA expression of STK33 in L9981 and NL9980 by RT-PCR-To construct the low transient expression plasmid of STK33 and transfected cells L9981, referred to as L9981 (-);Construction the high transient expression plasmid of STK33 and transfected cells NL9980,referred to as NL9980(+),Identified the result of transfection by RT-PCR.After successful transfection,to detect the protein expression of STK33 and important protein PAK1 and p38MAPK of Ras-MAPK signaling pathway in four cells by Western-blot;Analyzes the interaction of STK33 and the protein of PAK1-p and p38MAPK-p by CO-IP.Results:(1)In NL9980,the mRNA expression level of STK33 is is lower than L9981 (P<0.001);(2)Successfully constructed the high transient expression plasmid and low transient expression plasmid,which were transfected successfully.(3)In L9981(-),the protein expression of STK33 is lower than L9981;And in NL9980(+),the protein expression of STK33 is higher than NL9980.(4)When the protein expression of STK33 changed, the level of non-phosphorylated protein PAK1 and p38MAPK in Ras-MAPK signaling pathway was not little changed, the expression of phosphorylated proteins in L9981(-) was lower than L9981 and in NL9980 (+) was higher than NL9980.(5)Detect the interactions between STK33 and the phosphorylated proteins PAK1-p、 p38MAPK-p in Ras-MAPK signaling pathway by CO-IP,the results confirmed that STK33 and PAKl-p has no direct effect, but the p38MAPK-p may have a effect. Conclusion:STK33 differentially expressed in different metastatic lung cancer ce-lls,suggesting that it may be associated with staging and the degree of different-i ation of lung cancer.STK33 expression changes can cause the phosphorylated pr-oteins changed of PAKl-p and p38MAPK-p in Ras-MAPK signaling pathway.When STK33 high expression,the expression increased of phosphorylated proteins PAK1-p and p38MAPK-p,and may promote epithelial-mesenchymal transition (E MT),reduced apoptosis, suggesting that STK33 may be facilitate the transfer and invasion of NSCLC; Inhibit the expression of STK33 in human lung cancer ce-11s may be decline the metastasis of NSCLC.STK33 may become a new target for the treatment of NSCLC.