miR-106b-5p inhibits the invasion and metastasis of colorectal cancer by targeting CTSA
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 anonymous peer review
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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