PAK6 signaling attenuates migratory and invasive abilities of non-small cell lung cancer cells |
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Authors: | CAI Song-wang LI Dong-xia AN Jun ZHANG Jun-hang |
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Institution: | 1.Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; 2.Laboratory of Functional Science, Xinxiang Medical College, Xinxiang 453003, China. |
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Abstract: | AIM:To investigate the roles of p21-activated kinase 6 (PAK6) and its target miRNA on the migratory and invasive abilities of non-small cell lung cancer cells. METHODS:miRNA candidates targeting PAK6 were predicted by a target prediction program. The expression of PAK6 was measured by real-time PCR and Western blotting after A549 cells were transfected with miR-23a mimics or inhibitory oligonucleotides. Luciferase reporter assay was used to determine whether PAK6 was the direct target of miR-23a. The abilities of cell migration and invasion were detected by Matrigel invasion assay and Transwell migration assay. The expression of PAK6 and matrix metalloproteinase 9 (MMP-9) was analyzed by Western blotting after A549 cells were transfected with siPAK6 or miR-23a mimics. RESULTS:miR-23a was identified by a target prediction program. Exogenetic over-expression of miR-23a resulted in a remarkable decrease in PAK6 expression (69%), whereas miR-23a inhibitory oligonucleotides induced pronounced increase in PAK6 expression (52%). The luciferase activity was significantly inhibited by 52% in wild-type PAK6 group, while there was no significant difference in the mutation group. The mRNA level of PAK6 had no change as detected by real-time PCR. Matrigel invasion assay and Transwell migration assay demonstrated there exogenetic over-expression of miR-23a markedly reduced the migration and invasion of PC-3 cells (73% and 59%, respectively). The MMP-9 expression remarkably decreased by 85% and 76% in the A549 cells transfected with siPAK6 and miR-23a mimics, respectively. CONCLUSION:miR-23a inhibits the migration and invasion of non-small cell lung cancer cells by repressing PAK6-MMP-9 signaling pathway. |
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Keywords: | MicroRNA-23a p21-activated kinase 6 Matrix metalloproteinase 9 Non-small cell lung cancer |
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