Background: STAT3 (signal transducer and activator of transcription 3) has been reported to be an oncogenic transcription factor and high expression of STAT3 is associated with lung cancer progression. Recent studies demonstrate that STAT3 may control micrRNAs to promote cancer progression. RECK (reversion-inducing cysteinerich protein with Kazal motifs) is a tumor suppressor gene and a membrane-anchored glycoprotein that reduces the matrix metalloproteinases (MMPs)-induced destruction of extra-cellular matrix (ECM) and tumor metastasis. RECK also inhibits tumor angiogenesis. In this study, we try to elucidate whether ovexpression of STAT3 can affect microRNA expression to regulate RECK via post-transcriptional modulation. Methods: Regulation of miR-92a by STAT3 was studied by overexpression of constitutively active STAT3 or STAT3 inhibitors. 3’UTR reporter assay was performed to verify RECK is a miR-92a target. Pre-miR-92a and anti-miR-92a were used to study their roles in STAT3-mediated down-regulation of RECK. Transwell assays were carried out to show the effect of miR-92a on cell migration and invasion. Results: We found that miR-92a, a member of miR-17-92a cluster could target RECK 3’UTR. In addition, our data showed that STAT3 regulated the expression of miR-92a and inhibition of STAT3 significantly decreased miR-92a expression. Furthermore, miR-92a reduced RECK protein but not mRNA level. Knockdown of miR-92a expression in STAT3-overexpressing cell lines restored RECK protein level, and attenuated cell invasion and migration. Conclusion: Collectively, our results suggest that STAT3 up-regulates miR-92a to inhibit RECK expression and promote lung cancer metastasis.
Date:
2012-11
Relation:
Journal of Thoracic Oncology. 2012 Nov;7(11, Suppl. 5):S464.
