Over-expression of cofilin-1 regulates let-7 microRNA to suppress growth and invasion of human lung cancer cells

• Main Authors: Man-Jyun Liao, 廖曼均
• Other Authors: Yi-Jang Lee
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/95915478067254979540

碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 103 === Cancer is one of major causes of mortality in 20th century. The spread of cancer from the primary site to distant organs is the most life-threatening event caused by cancers, so called metastasis. Chemotherapy, radiotherapy and surgery are limited to against metastasis. Targeting on metastasis by better understanding the molecular mechanisms would be important for design of new therapeutic strategies. Cofilin-1 is an actin binding protein belonging to the actin depolymerizing factor (ADF)/cofilin family, which is important for accelerating actin dynamics for cell migration. We previously found that over-expressed cofilin-1 led to destabilization of actin cytoskeleton and inhibition of invasion in human non-small cells lung cancer. However, the underlying mechanisms remain unclear. The hsa-let 7 family is a type of microRNA that exhibits tumor suppressive property. MicroRNA is a non-coding RNA, but it plays a significant role in cancer. Using a tetracycline inducible system to over-express cofilin-1 in H1299 lung cancer cells, we found that let-7 family members were up-regulated by over-expressed cofilin-1 as determined by the microRNA microarray analysis. Let-7b and let-7e are mostly up-regulated when cofilin-1 was over-expressed in this stable cell line. Use of locked nucleic acid (LNA) to inhibit let-7b and let-7e in cofilin over-expressing cells could recover the cell growth and metastatic ability. Subsequently, the in vivo experimental metastasis model and luciferase reporter gene imaging was used to confirm that cofilin-1 over-expression suppressed lung metastasis can be suppressed by transfection of LNA targeting let-7. Twist-1, one of the let-7 regulating molecules, was also found to be suppressed by over-expressed cofilin-1. This study will be important to better understand the mechanisms of cofilin-1 mediated inhibition of tumor invasion, and will be important for considering design of new therapeutic strategy for cancer treatment.