A small slice of RNA inhibits prostate cancer metastasis by suppressing a surface protein commonly found on prostate cancer stem cells. miR-34a targets a surface protein common to cancer stem cells and associated with tumor development and metastasis. When the micro RNA stifles CD44, it inhibits formation of prostate stem cells. Researchers blocked tumor formation, shrunk tumors and inhibited metastasis in mouse models.
A research team led by scientists at The University of Texas MD Anderson Cancer Center reported January 16 in an advance online publication at Nature Medicine.
"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," said senior author Dean Tang, Ph.D., professor in MD Anderson's Department of Molecular Carcinogenesis.
MicroRNAs, or miRNAs, are short, single-stranded bits of RNA that regulate the messenger RNA expressed by genes to create a protein.
Cancer stem cells are capable of self-renewal, have enhanced tumor-initiating ability and are generally more resistant to treatment than other cancer cells. They are associated with tumor recurrence and metastasis, the lethal spreading of cancer to other organs. These capacities are more prevalent in cancer cells that feature a specific cell surface protein called CD44, Tang said.
"CD44 has long been linked to promotion of tumor development and, especially, to cancer metastasis," Tang said. "Many cancer stem cells overexpress this surface adhesion molecule. Another significant finding from our study is identifying CD44 itself as a direct and functional target of miR-34a."
MicroRNA goes up, CD44 and cancer stem cells fall.
In a series of lab experiments with cell lines, human xenograft tumors in mice and primary human prostate cancer samples, the researchers demonstrated that miR-34a inhibits prostate cancer stem cells by suppressing CD44.
"There are many companies developing microRNA-based drugs," Tang said. "Delivery of miRNAs is a challenge, but the field is moving fast through the preclinical stage."
Scientists from Austin-based Mirna Therapeutics collaborated on the study. Mirna has eight microRNAs in preclinical development, including miR-34a.
The project was funded in part by grants from the National Cancer Institute and the National Institute of Environmental Health Science, the U.S. Department of Defense and the Elsa Pardee Foundation.
Co-authors were first author Can Liu, Bigang Liu, M.D., Xin Chen, Tammy Calhoun-Davis, Hangwen Li, Ph.D., Hong Yan, Ph.D., Collene Jeter, Ph.D., and Sofia Honorio, Ph.D., all of MD Anderson's Department of Molecular Carcinogenesis at the Science Park in Smithville, Texas; Can Liu and Xin Chen are also students in The University of Texas Graduate School of Biomedical Sciences at Houston, jointly operated by MD Anderson and The University of Texas Health Science Center at Houston; Lubna Patrawala, Ph.D., Kevin Kelnar, Jason Wiggins, Andreas Bader, Ph.D., and David Brown, Ph.D., all of Mirna Therapeutics, Inc. and Randy Fagin, M.D., of The Hospital at Westlake, Austin, Texas.
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