RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2.
miR-205 reconstitution was able to significantly enhance the radiation response of prostate cancer cell lines and xenografts through the impairment of radiation-induced DNA damage repair, as a consequence of PKCε and ZEB1 inhibition.
The analysis of the data revealed that miR-21-5p, miR-141-3p, and miR-205-5p are differentially expressed in urine of bladder and prostate cancer patients.
miR-1825, miR-484, miR-205, miR-141, and let-7b were shown to be highly specific for PCa, suggesting that they could be used as PCa tumor screening biomarkers. miR-205 may also be used as a biomarker for indicating bone metastasis in PCa patients, miR-1825 levels may help indicate tumor-node-metastasis classification, the evaluation of treatment effects, and determining prognosis, while let-7b levels may indicate potential tumor malignancy and the hormone resistance status and could be used as a basis to adjust individual treatments for the high-risk, early diagnosis of refractory PCa.
We focused on high-mobility group box 3 (HMGB3) because it was the most downregulated by ectopic expression of miR-205-5p in PC3 cells and its expression was involved in PCa pathogenesis.
In conclusion, miR-205-5p inhibited cell migration and invasion in prostatic carcinoma by targeting ZEB1 and miR-205-5p/ZEB1 axis shows potential to be developed in therapeutic strategies for prostate cancer.
MicroRNAs (miRs) have emerged as important regulators of cellular pathways, resulting in altered gene expressions. miR-205 has previously been observed downregulated in PC, acting as tumor suppressor.
The miR-205/TP53INP1 mediated autophagy pathway might be an important molecular mechanism regulating radiosensitivity of prostate cancer cells and represents a potential therapeutic target for prostate cancer.
Urinary miR-183 and miR-205 do not surpass PCA3 in urine as predictive markers for prostate biopsy outcome despite their highly dysregulated expression in prostate cancer tissue.
Loss of tumor-suppressive microRNA-205 seems to enhance cancer cell migration and invasion in prostate cancer through direct regulation of centromere protein F. Our data describing pathways regulated by tumor-suppressive microRNA-205 provide new insights into the potential mechanisms of prostate cancer oncogenesis and metastasis.
We previously reported that miR-205 promotes apoptosis by targeting antiapoptotic protein Bcl-w and miR-205 is silenced in prostate cancer through promoter methylation.
Overall, our data indicate that (i) loss of miR-205 may indeed contribute to acquire mesenchymal tracts and concomitantly establish a permissive autophagic milieu that confers a chemotherapy resistant phenotype to prostate cancer cells, and (ii) strategies aimed at restoring miR-205 expression levels may represent a successful approach to overcome resistance of prostate cancer to platinum compounds.
Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma.
Consistent with its anti-apoptotic target BCL2, miR-205 promoted apoptosis in prostate cancer cells in response to DNA damage by cisplatin and doxorubicin in the prostate cancer cell lines PC3 and LnCap.
In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.
Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro.
Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression.
A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR-205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach.