title: miR-129-3p, as a diagnostic and prognostic biomarker for renal cell carcinoma, attenuates cell migration and invasion via downregulating multiple metastasis-related genes.
abstract: OBJECTIVE
  Downregulation of miRNA expression has been identified as a novel feature of renal cell carcinoma (RCC). Recently, miR-129-2 is well known to be frequently reduced by DNA methylation and has anti-tumor effects in various tumors but so far not in RCC. The aim of this study was to investigate the clinical significance and the role of it in RCC.
  
  
  METHODS
  The expression levels of miR-129-3p and miR-129-5p, two mature products of miR-129-2, were determined by real-time quantitative reverse transcription PCR in 69 cases of paired different kidney tumors and normal tissues and clear cell RCC (ccRCC) cell lines. The roles of them in RCC cells were assessed by functional analyses. Protein expression was detected by Western blot.
  
  
  RESULTS
  miR-129-3p, but not miR-129-5p, was widely attenuated in human ccRCC, and chromophobe RCC. miR-129-3p could yield 73.5 % accuracy in discriminating ccRCCs from normal tissues. The relative miR-129-3p expression significantly differed between malignant and benign kidney tumors. Importantly, low miR-129-3p levels were associated with short disease-free and overall survival. Ectopic expression of miR-129-3p robustly impaired RCC cell migratory and invasive properties, but had no impact on cell viability and cell cycle distribution. Finally, miR-129-3p decreased multiple metastasis-related genes in RCC cells, including SOX4, phosphorylation of focal adhesion kinase and MMP-2/9 expression.
  
  
  CONCLUSIONS
  miR-129-3p may act as a promising diagnostic biomarker for discriminating ccRCC from benign tumors and normal tissues and an independent prognostic biomarker in ccRCC. miR-129-3p may exert its anti-metastatic function through modulating multiple targets.
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People's Republic of China.
authors.forename: Xuanyu
authors.initials: X
authors.lastname: Chen
authors.forename: Anming
authors.initials: A
authors.lastname: Ruan
authors.forename: Xuegang
authors.initials: X
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Han
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Lou
authors.forename: Hailong
authors.initials: H
authors.lastname: Ruan
authors.forename: Bin
authors.initials: B
authors.lastname: Qiu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9