MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 29, 45199-45213 p.Article in journal (Refereed) Published
Background: Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. Results: miR-20a-5p negatively regulated Smad4 by directly targeting its 3UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Methods: Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. Conclusions: miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.
Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2016. Vol. 7, no 29, 45199-45213 p.
miR-20a-5p; colorectal cancer; metastasis; prognosis; Smad4
Cancer and Oncology
IdentifiersURN: urn:nbn:se:liu:diva-132548DOI: 10.18632/oncotarget.9900ISI: 000385402300029PubMedID: 27286257OAI: oai:DiVA.org:liu-132548DiVA: diva2:1046348
Funding Agencies|funds form National High Technology Research and Development Program of China [SS2014AA020803]; National Natural Science Foundation of China [81220108021, 81272750, 81530044]; Natural Science Foundation of Shanghai [16ZR1427700]; Project of Shanghai Science and Technology Commission ; Joint Research Projects of Shanghai Municipal Hospital [2013SY015]; Project of Songjiang District [0702N14001]; National Institutes of Health Grants of America [1R01CA166144]; CNAC NIMH [P30MH092177]2016-11-142016-11-132016-12-02