Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis.
OBJECTIVE
MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis.


METHODS
Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR.


RESULTS
miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P<0.001), (55.550 vs. 8.314, P=0.010), and (33.549 vs. 2.748, P=0.001), respectively.


CONCLUSIONS
We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 β3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies.
Leite
Katia R M
KR
Laboratory of Medical Investigation, LIM55, Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil. katiaramos@uol.com.br
Sousa-Canavez
Juliana M
JM
Reis
Sabrina T
ST
Tomiyama
Alberto H
AH
Camara-Lopes
Luiz H
LH
Sañudo
Adriana
A
Antunes
Alberto A
AA
Srougi
Miguel
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; C544266:MIRN100 microRNA, human; C547471:MIRN218 microRNA, human; D035683:MicroRNAs