MiR-106b-25 cluster targets caspase 7 and focal adhesion in human prostate cancer

ABSTRACT: We and others previously reported that the miR-106b-25 microRNA cluster is a candidate oncogene in human prostate cancer. Here, we made the novel observation that miR-106b-25 expression is further up-regulated in distant metastasis. Moreover, increased tumor miR-106b expression was associated with early disease recurrence. To identify yet unknown oncogenic functions of the prognostic miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that caspase-7 is a candidate direct target of miR-106b, which was confirmed by Western blot analysis and a 3’UTR reporter assay. Other analyses showed that caspase-7 is down-regulated in primary human prostate tumors and metastatic lesions across multiple datasets and is by itself associated with disease recurrence. Using bioinformatics, we also discovered that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally confirmed using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and metastasis and may do so by altering apoptosis- and focal adhesion-related pathways. To elucidate the effects miR-106b, we up-regulated miR-106b in LNCaP cells and examined gene expression alterations on a global scale with Affymetrix arrays.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34893 | GEO | 2012/05/01

SECONDARY ACCESSION(S): PRJNA150187

REPOSITORIES: GEO