Lung cancer is the common cause of cancer death. 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. RECK (reversion-inducing cysteine-rich 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. We have previously elucidated the transcriptional regulation of RECK gene. Recently, microRNAs (miRs) are shown to be key players in gene regulation and cancer progression. In this study, we try to elucidate whether ovexpression of STAT3 can affect microRNA expression to regulate RECK via post-transcriptional modulation. miR-17-92a cluster is a well-known oncomir which is highly expressed in lung cancer tissue. We find that miR-92a, a member of miR-17-92a cluster can target RECK 3¡¦UTR. In addition, our data suggest that STAT3 regulates the expression of miR-92a and inhibition of STAT3 can decrease miR-92a expression. Furthermore, overexpression of miR-92a can decrease RECK protein level. While knockdown of miR-92a expression in STAT3-overexpressing cell lines can restore RECK protein level, and reduce invasion and migration. Results of this study suggest that STAT3 up-regulates miR-92a to inhibit RECK expression and promote lung cancer metastasis.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0706112-173625 |
| Date | 06 July 2012 |
| Creators | Lin, Hsin-Ying |
| Contributors | Po-Lin Kuo, Kuang-Hung Cheng, Wen-Chun Hung |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0706112-173625 |
| Rights | user_define, Copyright information available at source archive |
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