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- Mi, Yushuai, et al.
(författare)
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miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation
- 2017
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Ingår i: Cancer Letters. - : ELSEVIER IRELAND LTD. - 0304-3835 .- 1872-7980. ; 389, s. 11-22
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Zhao, Senlin, et al.
(författare)
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miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGF beta-mediated epithelial to mesenchymal transition
- 2017
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Ingår i: Molecular Cancer. - : BIOMED CENTRAL LTD. - 1476-4598. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. Methods: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGF beta pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. Results: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGF beta signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/ Smad7/TGF beta in vitro and in vivo. Conclusion: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGF beta signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.
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