miR-106b-5p inhibits the invasion and metastasis of colorectal cancer by targeting CTSA
Authors Ni S, Weng W, Xu M, Wang Q, Tan C, Sun H, Wang L, Huang D, Du X, Sheng W
Received 2 May 2018
Accepted for publication 6 June 2018
Published 4 July 2018 Volume 2018:11 Pages 3835—3845
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr Carlos E Vigil
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
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