MicroRNA Expression Profiling in Prostate Cancer

Abstract

MicroRNAs (miRNA) are small, endogenously expressed noncoding RNAs that negatively regulate expression of proteincoding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they are involved in the development of cancer. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature specific for prostate cancer, miRNA expression profiling of 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, 4 benign prostatic hyperplasia (BPH), and 9 prostate carcinoma samples was carried out by using an oligonucleotide array hybridization method. Differential expression of 51 individual miRNAs between benign tumors and carcinoma tumors was detected, 37 of them showing down-regulation and 14 up-regulation in carcinoma samples, thus identifying those miRNAs that could be significant in prostate cancer development and/or growth. There was a significant trend (P = 0.029) between the expression of miRNAs and miRNA locus copy number determined by array comparative genomic hybridization, indicating that genetic aberrations may target miRNAs. Hierarchical clustering of the tumor samples by their miRNA expression accurately separated the carcinomas from the BPH samples and also further classified the carcinoma tumors according to their androgen dependence (hormone naive versus hormone refractory), indicating the potential of miRNAs as a novel diagnostic and prognostic tool for prostate cancer. [Cancer Res 2007;67(13):6130-5]

Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma?

“…In other words, a tumor tissue sample may include normal or benign prostate hyperplasia tissue even though a microdissection was performed to include over 90% of the tumor based on H&E stain preparation. 10,11 In our study, we also tried to include over 90% of the tumor through H&E stain preparation.…”

“…2,11 A diagnostic hematoxylin and eosin (H&E) section was prepared to verify tumor content and margin status, and to identify areas of normal and tumor tissue. After the pathologist marked the portion that contained more than 90% tumor tissue, another formalin-fixed, paraffin-embedded sample containing this portion was prepared, using a microtome for RNA extraction.…”

“…[5][6][7][8] However, to date, few articles have investigated miRNA regulation in prostate cancer and only five studies have examined miRNA expression in more than 10 samples, with highly inconsistent results. 2,[9][10][11][12][13] Schaefer et al 4 reported that there is no overlapping subset between the down-and upregulated miRNA patterns of previous studies. In addition, 17 of the 105 types of miRNA even showed an opposite expression pattern.…”

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression

“…26 Abundant expression of miR-200a has been also shown in some prostate cancer cell lines. 14 It is notable that measurement of tumor-derived miRNAs in serum or plasma is now possible; the serum level of miR-141 could be a potential diagnostic marker in prostate cancer. 26 Whether miR-148a could also be a useful biomarker in prostate cancer is a subject for future study.…”

“…12 Recently, miRNA profiling has been reported to be informative and predictive in some malignancies, including prostate cancer. [13][14][15] Systematic identification of disease-associated miRNAs will be useful for finding good indicators for prostate cancer management, although a consensus has not been yet achieved in terms of a prostate cancerrelated miRNA signature.…”