Role of Periostin Expression in Non-Small Cell Lung Cancer: Periostin Silencing Inhibits the Migration and Invasion of Lung Cancer Cells via Regulation of MMP-2 Expression

Periostin 表达在非小细胞肺癌中的作用:Periostin 沉默通过调节 MMP-2 表达抑制肺癌细胞的迁移和侵袭

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作者:Katarzyna Ratajczak-Wielgomas, Alicja Kmiecik, Piotr Dziegiel

Abstract

The involvement of periostin (POSTN) in non-small-cell lung cancer (NSCLC) migration, invasion, and its underlying mechanisms has not been well established. The present study aims to determine epithelial POSTN expression in NSCLC and to assess associations with clinicopathological factors and prognosis as well as to explore the effects of POSTN knockdown on tumor microenvironment and the migration and invasion of lung cancer cells. Immunohistochemistry was used to evaluate epithelial POSTN expression in NSCLC. POSTN mRNA expression in the dissected lung cancer cells was confirmed by laser capture microdissection and real-time PCR. A549 cells were used for transfecting shRNA-POSTN lentiviral particles. Wound healing and Transwell invasion assays were used to assess the migratory and invasive abilities of A549 cells transfected with POSTN-specific short hairpin (sh)RNA. The results demonstrated significantly higher cytoplasmic POSTN expression in the whole NSCLC group compared to non-malignant lung tissue (NMLT). POSTN expression in cancer cells may be considered to be an independent prognostic factor for survival in NSCLC. POSTN knockdown significantly inhibited A549 cell migration and invasion capabilities in vitro. The activity and the expression level of matrix metalloproteinase-2 (MMP-2) were significantly decreased in A549.shRNA compared to control cells. In summary, POSTN may regulate lung cancer cell invasiveness by modulating the expression of MMP-2 and may represent a potential target for novel therapeutic intervention for NSCLC.

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