title: MiR-323 Inhibits Prostate Cancer  Vascularization Through Adiponectin  Receptor.
abstract: OBJECTIVE
  The current treatments fail to provide satisfactory cure for aggressive prostate cancers (PCs). Hence, further comprehension of PC metastasis is highly appreciated for improving the levels of therapy. We have previously shown that Adiponectin reduces the levels of vascular endothelial growth factor A (VEGF-A) in PCs to suppress tumor-associated neovascularization, possibly through AMPK/mTor signaling. Here, we studied the regulation of Adiponectin signaling in PCs.
  
  
  METHODS
  We analyzed the levels and correlation of Adiponectin receptor 1 (AdipoR1) and microRNA-323 (miR-323) in the PC specimen, compared to the paired normal prostate tissue. We analyzed the binding of miR-323 to the 3'UTR of AdipoR1 mRNA and its effects on AdipoR1 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-323 levels in PC cells, and examined the effects on the expression of AdipoR1 and VEGF-A, as well as on vessel formation in a human umbilical vein endothelial cells (HUVECs) transwell collagen gel assay.
  
  
  RESULTS
  We detected significantly lower levels of AdipoR1 and significantly higher levels of miR-323 in PC specimen. Moreover, the levels of AdipoR1 and miR-323 are inversely correlated. Moreover, miR-323 was found to bind to the 3’UTR of AdipoR1 mRNA to inhibit its translation. Overexpression of miR-323 in PC cells decreased AdipoR1 protein levels, whereas inhibition of miR-323 increased AdipoR1 protein levels, without affecting AdipoR1 transcripts. Moreover, overexpression of miR-323 increased the levels of VEGF-A and the vessel formation by HUVECs, while inhibition of miR- 323 decreased the levels of VEGF-A and the vessel formation by HUVECs.
  
  
  CONCLUSIONS
  Our data demonstrate that miR-323 may increase VEGF-A-mediated cancer vascularization in PC cells through AdipoR1 suppression.
authors.forename: Qiruo
authors.initials: Q
authors.lastname: Gao
authors.forename: Xudong
authors.initials: X
authors.lastname: Yao
authors.forename: Junhua
authors.initials: J
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054419:Receptors, Adiponectin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C475418:ADIPOR1 protein, human; C573188:MIRN323 microRNA, human; D035683:MicroRNAs; D054419:Receptors, Adiponectin; D042461:Vascular Endothelial Growth Factor A