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miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation
Shanghai Jiao Tong University, Peoples R China.
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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2017 (English)In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 389, 11-22 p.Article in journal (Refereed) Published
Abstract [en]

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2017. Vol. 389, 11-22 p.
Keyword [en]
miR-181a-5p; RASSF6; MAPK; Gastric cancer progression
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-136577DOI: 10.1016/j.canlet.2016.12.033ISI: 000395846100002PubMedID: 28043911OAI: oai:DiVA.org:liu-136577DiVA: diva2:1090304
Note

Funding Agencies|National High Technology Research and Development Program of China [SS2014AA020803]; National Natural Science Foundation of China [81272750, 81302083]

Available from: 2017-04-24 Created: 2017-04-24 Last updated: 2017-05-21

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Cui, WeiyingqiSun, Xiao-Feng
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Department of Orthopaedics in LinköpingDivision of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Oncology
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