miR-21: an oncomir on strike in prostate cancer

Abstract

BackgroundAberrant expression of microRNAs, small non-coding RNA molecules that post-transcriptionally repress gene expression, seems to be causatively linked to the pathogenesis of cancer. In this context, miR-21 was found to be overexpressed in different human cancers (e.g. glioblastoma, breast cancer). In addition, it is thought to be endowed with oncogenic properties due to its ability to negatively modulate the expression of tumor-suppressor genes (e.g. PTEN) and to cause the reversion of malignant phenotype when knocked- down in several tumor models. On the basis of these findings, miR-21 has been proposed as a widely exploitable cancer-related target. However, scanty information is available concerning the relevance of miR-21 for prostate cancer. In the present study, we investigated the role of miR-21 and its potential as a therapeutic target in two prostate cancer cell lines, characterized by different miR-21 expression levels and PTEN gene status.ResultsWe provide evidence that miR-21 knockdown in prostate cancer cells is not sufficient per se i) to affect the proliferative and invasive potential or the chemo- and radiosensitivity profiles or ii) to modulate the expression of the tumor-suppressors PTEN and Pdcd4, which in other tumor types were found to be regulated by miR-21. We also show that miR-21 is not differently expressed in carcinomas and matched normal tissues obtained from 36 untreated prostate cancer patients subjected to radical prostatectomy.ConclusionsOverall, our data suggest that miR-21 is not a central player in the onset of prostate cancer and that its single hitting is not a valuable therapeutic strategy in the disease. This supports the notion that the oncogenic properties of miR-21 could be cell and tissue dependent and that the potential role of a given miRNA as a therapeutic target should be contextualized with respect to the disease.

Identification of Novel miR-21 Target Proteins in Multiple Myeloma Cells by Quantitative Proteomics

“…15 miR-21 is a unique miRNA in that it is overexpressed in the vast majority of cancer types analyzed so far 16 and has thus been recognized as an oncomiR. 17 Inhibition of miR-21 was shown to cause decreased cell growth in vitro and decreased tumor growth in a xenograft mouse model, 18 increased apoptosis and reduced invasiveness in glioblastoma, 19 and reduced cell proliferation, migration and tumor growth in breast cancer. 20 Recently, Medina et al showed that overexpression of miR-21 leads to a pre-B malignant lymphoid-like phenotype and that inhibiting miR-21 alone induces complete tumor regression in a few days, demonstrating that miR-21 is a central oncomiR in tumor formation.…”

Genomic and Epigenomic Alterations in Cancer

“…69 Conversely, miR-155 acts as an oncogene by affecting the recombination process via cytidine deaminase, 70 and is up-regulated in breast and lung cancers. Oncomir MIR21 is overexpressed in breast cancer, 71 glioblastoma, 72 prostate cancer, 73 and others. miR10b is known to regulate breast cancer metastasis.…”

Is Use of Micro-RNA–Containing Food Feasible?

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