title: The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer.
abstract: OBJECTIVE
  The aim of this study is to verify the expression of proteins that are controlled by miR-let7c, 100 and 218 using immunohistochemistry in tissue microarray representative of localized and metastasized the lymph nodes and bone prostate cancer.
  
  
  METHODS
  To verify the expression of proteins that are controlled by miR-let7c (C-MYC, BUB1, RAS) 100 (SMARCA5, RB) and 218 (LAMB3) and cell proliferation (Ki-67) we used immunohistochemistry and computerized image system ImageJ MacBiophotonics in three tissue microarrays representative of localized prostate cancer and lymph node and bone metastases. miRNA expression was evaluated by qRT-PCR using 60 paraffin blocks to construct the tissue microarray representative of localized disease.
  
  
  RESULTS
  RAS expression was increased in localized prostate cancer and bone metastases compared to the lymph nodes (p=0.017). RB showed an increase in expression from localized prostate cancer to lymph node and bone metastasis (p=0.036). LAMB3 was highly expressed in localized and lymph node metastases (p<0.001). Cell proliferation evaluated by Ki-67 showed an increase from localized prostate cancer to metastases (p<0.001). We did not found any relationship between C-MYC (p=0.253), BUB1 (p=0.649) and SMARCA5 (p=0.315) protein expression with prognosis or tumor behavior.
  
  
  CONCLUSIONS
  We found that the expression of RAS, RB, LAMB3 and Ki-67 changed in the different stages of prostate cancer. Furthermore, we confirmed the overexpression of the miRNAs let7c, 100 and 218 in localized prostate cancer but failed to show the control of protein expression by the putative controller miRNAs using immunohistochemistry.
authors.affiliation: Faculdade de Medicina da Universidade de São Paulo, Urology Department, Laboratory of Medical Research, LIM55, São Paulo/SP, Brazil.
authors.forename: Sabrina T
authors.initials: ST
authors.lastname: Reis
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Timoszczuk
authors.forename: José
authors.initials: J
authors.lastname: Pontes-Junior
authors.forename: Nayara
authors.initials: N
authors.lastname: Viana
authors.forename: Iran A
authors.initials: IA
authors.lastname: Silva
authors.forename: Nelson
authors.initials: N
authors.lastname: Dip
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
authors.forename: Katia R M
authors.initials: KR
authors.lastname: Leite
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D001859:Bone Neoplasms / Q000556:secondary*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D000097794:Kalinin
chemical_list: D000251:Adenosine Triphosphatases; D015815:Cell Adhesion Molecules; D002868:Chromosomal Proteins, Non-Histone; D019394:Ki-67 Antigen; D035683:MicroRNAs; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D016271:Proto-Oncogene Proteins c-myc; D016283:Proto-Oncogene Proteins p21(ras); D016160:Retinoblastoma Protein; D000097794:Kalinin; C544266:MIRN100 microRNA, human; C547471:MIRN218 microRNA, human; C489427:MYC protein, human; C487931:mirnlet7 microRNA, human; C584277:BUB1 protein, human; C409462:SMARCA5 protein, human