title: MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis.
abstract: 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.
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yuekun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sui
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Daxun
authors.initials: D
authors.lastname: Piao
authors.affiliation: Department of Digestive Disease, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Sha
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002645:Chickens; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D050779:Nuclear Factor 90 Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: C568221:MIRN590 microRNA, human; D035683:MicroRNAs; D050779:Nuclear Factor 90 Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A