We present a molecular mechanism in which EGFR activation leads to the induction of miR-96 expression and suppression of ETV6, which contributes to prostate cancer progression.
To investigate the expression of miR-96 and related target genes in the regulation of prostatic cancer, we compared the expression of miR-96 in both prostatic cancer and adjacent normal tissues, and explored the role of miR-96 in prostate cancer.
Overexpressing miR-96 led to increased proliferation and colony formation of normal prostate epithelial cells. miR-96 level was found to be inversely associated with the abundance of metastasis suppressor protein 1 (MTSS1) messenger RNA (mRNA), which has been proved to be a tumor suppressor for PC.
Here, we demonstrate that TGFβ regulates the level of microRNA-96 (miR-96) through Smad-dependent transcription and that miR-96 promotes the bone metastasis in prostate cancer.
Our findings also suggest that miR-133a/MCL1, miR-513c/STAT1, and miR-96/FOXO3A may have clinical significance in the development of novel strategies for treating aggressive prostate cancer.
Inhibition of miR-96 caused expression increase of tumor suppressor gene FOXO1, thus manipulating miR-96 expression may be a promising approach in treatment of prostate cancer.
Taken together these findings indicate that miR-96 plays a key role in prostate cancer cellular proliferation and can enhance prostate cancer progression.