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miR-106b-5p inhibits the invasion and metastasis of colorectal cancer by targeting CTSA
- Source :
- OncoTargets and Therapy, Vol Volume 11, Pp 3835-3845 (2018)
- Publication Year :
- 2018
- Publisher :
- Dove Medical Press, 2018.
-
Abstract
- Shujuan Ni,1,2,* Weiwei Weng,1,2,* Midie Xu,1,2 Qifeng Wang,1,2 Cong Tan,1,2 Hui Sun,1,2 Lei Wang,1,2 Dan Huang,1,2 Xiang Du,1,2 Weiqi Sheng1,2 1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China *These authors contributed equally to this work Background: Although miR-106b-5p has been reported to play a pivotal role in various human malignancies, its role in colorectal cancer (CRC) remains unknown. In this study, we comprehensively investigated miR-106b-5p expression and biologic functions in CRC and the molecular mechanism involved. Patients and methods: miR-106b-5p expression was detected in CRC tissues and cell lines by quantitative reverse transcription-polymerase chain reaction. The effects of miR-106b-5p on metastasis were determined in vitro using transwell assays, and in vivo effects were evaluated using a mouse tail vein injection model. Downstream targets of miR-106b-5p were confirmed using bioinformatics programs, luciferase assays, and rescue experiments. Target gene expression and clinicopathologic parameters were also analyzed. Results: miR-106b-5p expression was lower in CRC tissues than in corresponding nontumorous tissues (P=0.009), and miR-106b-5p downregulation was negatively associated with lymph node metastasis (P=0.006). Functional assays demonstrated that miR-106b-5p overexpression suppressed CRC cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, luciferase assays confirmed that miR-106b-5p directly bound to the 3' untranslated region of cathepsin A (CTSA) and that miR-106b-5p suppressed CRC cell migration and invasion by targeting CTSA. Clinicopathologic analysis showed that CTSA was significantly upregulated in CRC, and increased CTSA was negatively associated with lymph node metastasis (P=0.012). Conclusion: Our findings revealed that miR-106b-5p inhibits CRC metastasis by upregulating CTSA expression, which may lead to novel therapeutic strategies for CRC patients. Keywords: colorectal cancer, metastasis, miR-106b-5p, cathepsin A
Details
- Language :
- English
- ISSN :
- 11786930
- Volume :
- ume 11
- Database :
- Directory of Open Access Journals
- Journal :
- OncoTargets and Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7edda7d5e9ce4cd78586d7d4d3e42edc
- Document Type :
- article