MiR-203 Inhibits Lung Cancer Cell Metastasis By Targeting FABP4

Obiective:According to the latest domestic tumor survey data,lung cancer is still the highest incidence of malignant tumors in China.The current treatment of lung cancer significantly increased the clinical efficacy significantly improved,but due to its high metastatic disease led to the survival and prognosis is still not ideal.Therefore,to further explore the mechanism of lung cancer metastasis is the current focuslung of cancer diagnosis and treatment.Fatty acid binding protein 4(FABP4)is an important protein of intracellular fatty acid metabolism.Recent studies have found that it can also promote the proliferation and metastasis of cervical cancer,liver cancer and other cells.Other study also found that there was a closely related between with the expression level of FABP4 and lung cancer prognosis,but the effect of FABP4 to lung cancer metastasis hasn't reported.microRNAs(miRNAs)are important factors in the regulation of intracellular protein expression.It is seldom reported whether miRNAs affect the metastasis of lung cancer by regulating FABP4 expression.Therefore,this study refers to the impact of FABP4 on metastasis of lung cancer cells and the miRNAs targeting FABP4.MethodsThe expression of FABP4 in lung cancer cells with different metastatic potential was detected by western blot.The expression of FABP4 in the supernatant of lung cancer cells with different metastatic potential was detected by ELISA.FABP4 expression was knocked down by shRNA or lentivirus over-expressed FABP4,and its effect on lung cancer cell metastasis was observed.The miRNAs targeting FABP4 were predicted by the miRNA data website and their expression in lung cancer cells with different metastatic potential was tested by Q-PCR.At the same time,FABP4-targeted miRNAs were transfected into FABP4-overexpressing lung cancer cells and their effects on FABP4 expression were observed.A miRNA was selected based on the expression of different metastatic lung cancer cells and inhibition of FABP4 expression,and further its site of targeting FABP4 was detected by point mutation and luciferase reporter system.Finally,miRNAs were overexpressed in lung cancer cells overexpressing FABP4 and miRNAs were down-regulated in lung cancer cells expressing FABP4,and their effects on lung cancer metastasis were observed.Results1.L9981,A549 and PC 13 with low metastasis ability were significantly increased in high metastatic lung cancer cells NL9980,H661,and 95C(P<0.05).On the other hand,in high metastatic lung cancer cells NL9980,H661 and 95C In Qingzhong FABP4,the L9981,A549 and PC 13 were significantly increased(P<0.05).2.The expression of FABP4 in NL9980 cells was knocked down by shRNA method,and the metastatic ability of NL9980 cells was significantly inhibited(P<0.05).However,the metastatic potential of A549 cells was significantly increased after over-expressing FABP4 by lentivirus(P<0.05).3.miR-203,miR-361 and miR-539 were significantly decreased in highly metastatic lung cancer cells NL9980,H661 and 95C(P<0.05),and miR-203 inhibited the expression of FABP4 in NL9980 cells the strongest expression(P<0.05).4.miR-203 targeted FABP43'-UPR end of the site is 270-282,transfected with targeted site mutation FABP4,miR-203 can not inhibit its expression.5.Overexpression of FABP4 protein targeting FABP4 mutation could reduce the inhibitory effect of miR-203 on the metastasis ability of NL9980 cells(P<0.05),and inhibit the expression of miR-203 in A549 cells(P<0.05).Conclusion1.FABP4 expression is increased in highly metastatic lung cancer cells,which promotes lung cancer cell metastasis.2.miR-203 inhibites lung cancer cell metastasis by targeting and inhibiting FABP4 expression.