A group of researchers have demonstrated that miR-34a inhibits prostate cancer tumor-initiating cells by suppressing CD44, a cell surface protein prevalent on cancer cells. The research was conducted by scientists at the University of Texas MD Anderson Cancer Center and Mirna Therapeutics. miR-34a is one of eight miRNAs in preclinical development by the company.
“Our findings are the first to profile a microRNA expression pattern in prostate cancer stem cells and also establish a strong rationale for developing the microRNA miR-34a as a new treatment option for prostate cancer,” says senior author, Dean Tang, Ph.D., professor in MD Anderson's department of molecular carcinogenesis.
The paper, “The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44,” is published in Nature Medicine.
The study demonstrated that miR-34a was under-expressed in CD44+ prostate cancer cells purified from xenograft and primary tumors. Enforced expression of miR-34a in bulk or purified CD44+ prostate cancer cells inhibited clonogenic expansion, tumor regeneration, and metastasis.
When miR-34a antagomirs were expressed in CD44- cancer cells, tumor development and metastasis was promoted. Also, when miR-34a was systemically delivered, it inhibited prostate cancer metastasis and extended the survival of tumor-bearing mice. The researchers concluded that miR-34a is a key negative regulator of CD44+ prostate cancer cells.
“CD44 has long been linked to promotion of tumor development and, especially, to cancer metastasis,” says Dr. Tang. “Many cancer stem cells over-express this surface adhesion molecule. Another significant finding from our study is identifying CD44 itself as a direct and functional target of miR-34a.”