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MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4
Shanghai Jiao Tong University, Peoples R China.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Shanghai Jiao Tong University, Peoples R China.
Shanghai Jiao Tong University, Peoples R China.
Shanghai Jiao Tong University, Peoples R China.
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2016 (Engelska)Ingår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 29, s. 45199-45213Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
IMPACT JOURNALS LLC , 2016. Vol. 7, nr 29, s. 45199-45213
Nyckelord [en]
miR-20a-5p; colorectal cancer; metastasis; prognosis; Smad4
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:liu:diva-132548DOI: 10.18632/oncotarget.9900ISI: 000385402300029PubMedID: 27286257OAI: oai:DiVA.org:liu-132548DiVA, id: diva2:1046348
Anmärkning

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 [14411950502]; Joint Research Projects of Shanghai Municipal Hospital [2013SY015]; Project of Songjiang District [0702N14001]; National Institutes of Health Grants of America [1R01CA166144]; CNAC NIMH [P30MH092177]

Tillgänglig från: 2016-11-14 Skapad: 2016-11-13 Senast uppdaterad: 2019-02-05

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