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.
The down-regulation of miR-145 has been reported in many types of human cancer, including prostate cancer (PC), suggesting that miR-145 functions as a tumor suppressor.
Here, we reported that miR-145 was silenced through DNA hypermethylation and p53 mutation status in laser capture microdissected (LCM) prostate cancer and matched adjacent normal tissues.
Collectively, these findings demonstrate that miR-143 and miR-145 inhibit CSC properties of PC-3 cells and suggest that miR-143 and miR-145 may play a significant role in the bone metastasis progression of PCa by regulating CSC characteristics.
These results suggest that loss of WT-p53 may promote the bone metastasis of PCa at least partially through repressing miR-145 to elevate EMT and stemness of cancer cells.
The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels.
We identify that TGFβ1-related miR-143, miR-145, miR-146a, and miR-199a may have a key role in the development of prostate cancer metastasis and the restoration of their expression may be a promising therapeutic strategy for PC treatment.
Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples.
These results suggest that the double-negative feedback loop between ZEB2 and miR-145 contributes to PCa progression and metastasis and might have therapeutic relevance for the bone metastasis of PCa.
To solve this problem, we inserted miRNA response elements (MREs), miR-143 and miR-145, expression levels of which were reduced in prostate carcinoma, as well as that of miR-122, which is specifically expressed in hepatic cells, into adenoviral vectors to control TRAIL expression (Ad-TRAIL-M3). qPCR data confirmed that miR-143, miR-145, and miR-122 levels were all decreased in prostate carcinoma cell lines and prostate cancer samples from patients.
Restoration of miR-143 or miR-145 in PCa cell lines (PC3 and DU145) revealed that these miRNAs significantly inhibited cancer cell migration and invasion.
Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer.
We aimed to perform functional analysis of miR-145-5p in prostate cancer (PCa) cells and to identify targets of miR-145-5p for understanding its role in PCa pathogenesis.
Rescue experiments demonstrated that miR-145-5p restoration attenuated the promotive effects of PCAT1 on PC progression, while Fascin-1 (FSCN1) upregulation relieved the anti-cancer role of miR-145-5p in PC.