Our results suggest that miR-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27(Kip1), and that their overexpression might be one of the factors contributing to the oncogenesis and progression of prostate carcinoma through p27(Kip1) down-regulation.
Specific capture and detection of mature miR-221 from complex samples was demonstrated in total RNA isolated from human prostate cancer cell lines and xenografts.
Further studies on a new mechanism of ARHI downregulation showed a significant inverse relationship between ARHI and miR-221 and 222, which were upregulated in prostate cancer cell lines.
In this work, we report that the ectopic modulation of NF-kB modifies miR-221/222 expression in prostate carcinoma and glioblastoma cell lines, where we had previously shown their oncogenic activity.
In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases. miRNA expression was determined using quantitative real-time polymerase chain reaction.
The performance of miRNAs 21 and 221 in differentiating prostate cancer from nonmalignant cases was evaluated and compared to DRE and elevated PSA. miRNA 21 was overexpressed in 90 % of group A vs. 10 % of group B, while miRNA 221 was overexpressed in 80 % of group A vs. 20 % of group B (p = 0.001).
Unexpectedly it was found that treatment with the AR agonists resulted in the repression of miR-221, a miRNA previously established to be involved with prostate cancer development.
In addition, a negative correlation was observed between the expressions of miR-221/222 and caspase-10 in prostate cancer cells. miR-221/222 could repress the expression of caspase-10, which was confirmed by the luciferase reporter assay.
Comparing with the other 18 types of cancers listed in The Cancer Genome Atlas Data Portal, we found that the combination of both miRNA-182 and miRNA-200c being up-regulated and miRNA-221 being down-regulated only happens in prostate cancer.
RESULTS A total of 162 miRNAs were differentially expressed between normal and prostate cancer samples, including 128 up-regulated and 38 down-regulated ones; hsa-mir-153-2, hsa-mir-92a-1, and hsa-mir-182 (up-regulated); and hsa-mir-29a, hsa-mir-10a, and hsa-mir-221 (down-regulated) were identified as good biomarkers.
Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH.
The aim of our study was to evaluate the relationship of TMPRSS2-ERG fusion gene status, tumor tissue prostate-specific antigen (PSA), prostate cancer antigen 3 (PCA3), miR-23b, miR-26a and miR-221 expression levels in combination with preoperative serum PSA level to the risk of PCa recurrence after radical prostatectomy.
As miR-221 targets several regulators of the PI3K-AKT-mTOR pathway and a link between this pathway and CD44 has been previously shown in prostate cancer, we considered miR-221 regulation of CD44 may be through this pathway.
Derepression of miR-221/-222 after androgen deprivation therapy (ADT) may enhance PCa cell proliferation potential through promoting G1/S phase transition.
Up-regulation and silencing of miR-221-5p expression in prostate cancer cells are correlated with cell proliferation, migration and tumorigenesis, which suggest that miR-221-5p plays an important role in prostate cancer progression.