Targeting MicroRNAs May Halt Metastatic Cascade at an Early Stage in Prostate Cancer

A new study is suggesting that by targeting a specific microRNA molecule (miR-141) it may be possible to stop the cascade of events that lead to metastasis in men with prostate cancer. Researchers at Roswell Park Cancer Institute report in the journal Nature Communications that miR-141 employs multiple mechanisms to obstruct tumor growth and metastasis.  

MicroRNAs are small genetic molecules that play an essential role in regulating many aspects of cancer cell behavior. When the researchers performed a screening of the miRNA library, they found that surprisingly only a few microRNAs are commonly deficient or not expressed in prostate cancer stem cells. 

The researchers examined the role of prostate cancer stem cells in promoting tumor growth and metastasis. They found that miR-141, which is one of the miR-200 family members, appears to be underexpressed in several prostate cancer stem/progenitor cell populations in both xenograft and primary patient tumors. The current study demonstrated that miR-141 is able to suppress prostate tumor growth and metastasis by targeting a cohort of prometastasis genes, including CD44, EZH2, and Rho GTPases.

“This study represents the most comprehensive investigation to date of the role of the miR-141 molecule in regulating prostate cancer stem cells and their role in metastasis,” said senior study author Dean Tang, PhD, who is Chair of the Department of Pharmacology and Therapeutics at Roswell Park Cancer Institute in Buffalo.

The study showed that miR-141 expression adds to a strong epithelial phenotype with a partial loss of mesenchymal phenotype. After conducting the whole-genome RNA sequencing, the researchers discovered novel miR-141-regulated molecular targets in prostate cancer cells. These included the Rho GTPase family members and stem cell molecules CD44 and EZH2.

Taken together with the findings from previous studies reporting the molecule’s powerful tumor suppression capability, the current study demonstrates the potential of miR-141 as an inhibitor of prostate cancer cell invasion and metastasis. Investigators theorize that a synthetic miR-141 agent could be developed to prevent prostate cancer metastasis in a way never before possible.

“These preliminary findings suggest that miR-141 may suppress the metastatic cascade at an early stage and that the overexpression of miR-141 in prostate cancer cells results in less metastasis. Our observations provide a rationale for developing these targeted miRNA molecules into novel antitumor and antimetastasis replacement therapies,” said Tang.