PMID- 27735951 OWN - NLM STAT- MEDLINE DCOM- 20170731 LR - 20240326 IS - 2041-4889 (Electronic) VI - 7 IP - 10 DP - 2016 Oct 13 TI - MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis. PG - e2413 LID - 10.1038/cddis.2016.306 [doi] AB - Altered expression of microRNA-590-5p (miR-590-5p) is involved in tumorigenesis, however, its role in colorectal cancer (CRC) remains to be determined. In this study, we focused on examining the effects of different expression levels of miR-590-5p in cancer cells and normal cells. Results showed that there are lower expression levels of miR-590-5p in human CRC cells and tissues than in normal control cells and tissues. Similarly, in our xenograft mouse model, knockdown of miR-590-5p promoted the progression of CRC. However, an overexpression of miR-590-5p in the mice inhibited angiogenesis, tumor growth, and lung metastasis. Nuclear factor 90 (NF90), a positive regulator of vascular endothelial growth factor (VEGF) mRNA stability and protein synthesis, was shown to be a direct target of miR-590-5p. The overexpression of NF90 restored VEGFA expression and rescued the loss of tumor angiogenesis caused by miR-590-5p. Conversely, the NF90-shRNA attenuated the increased tumor progression caused by the miR-590-5p inhibitor. Clinically, the levels of miR-590-5p were inversely correlated with those of NF90 and VEGFA in CRC tissues. Furthermore, knockdown of NF90 lead to a reduction of pri-miR-590 and an increase of mature miR-590-5p, suggesting a negative feedback loop between miR-590-5p and NF90. Collectively, these data establish miR-590-5p as an anti-onco-miR that inhibits CRC angiogenesis and metastasis through a new mechanism involving NF90/VEGFA signaling axis, highlighting the potential of miR-590-5p as a target for human CRC therapy. FAU - Zhou, Qingxin AU - Zhou Q AD - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Zhu, Yuekun AU - Zhu Y AD - Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Wei, Xiaoli AU - Wei X AD - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Zhou, Jianhua AU - Zhou J AD - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Chang, Liang AU - Chang L AD - Department of Neurosurgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Sui, Hong AU - Sui H AD - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Han, Yu AU - Han Y AD - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Piao, Daxun AU - Piao D AD - Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Sha, Ruihua AU - Sha R AD - Department of Digestive Disease, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, China. FAU - Bai, Yuxian AU - Bai Y AD - Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161013 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (MIRN590 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Nuclear Factor 90 Proteins) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Animals MH - Carcinogenesis/genetics/pathology MH - Cell Line, Tumor MH - Chickens MH - Colorectal Neoplasms/*blood supply/*genetics/pathology MH - Down-Regulation/genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - HEK293 Cells MH - Human Umbilical Vein Endothelial Cells/metabolism MH - Humans MH - Male MH - Mice, SCID MH - MicroRNAs/genetics/*metabolism MH - Middle Aged MH - Neoplasm Metastasis MH - Neovascularization, Pathologic/*genetics/pathology MH - Nuclear Factor 90 Proteins/*genetics/metabolism MH - *Signal Transduction MH - Survival Analysis MH - Vascular Endothelial Growth Factor A/*genetics/metabolism PMC - PMC5133975 EDAT- 2016/10/14 06:00 MHDA- 2017/08/02 06:00 PMCR- 2016/10/01 CRDT- 2016/10/14 06:00 PHST- 2016/04/07 00:00 [received] PHST- 2016/08/16 00:00 [revised] PHST- 2016/08/31 00:00 [accepted] PHST- 2016/10/14 06:00 [entrez] PHST- 2016/10/14 06:00 [pubmed] PHST- 2017/08/02 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - cddis2016306 [pii] AID - 10.1038/cddis.2016.306 [doi] PST - epublish SO - Cell Death Dis. 2016 Oct 13;7(10):e2413. doi: 10.1038/cddis.2016.306.