Recently, methods were developed to induce skin cells in our body to form embryonic-like stem cells, which have potential to become different types of cells; these cells are referred to as induced pluripotent stem cells (iPSCs). We asked the question whether microRNA (miRNA), small non-coding RNA used to be called "junk genes" but recently found to play an important role in modulating gene function, can also reprogram cells in our body to form iPSCs. The miRNA method is direct, fast, and more efficient. Indeed, our previous work has shown that the introduction of a family of miRNA, mir-302s, reverted human skin and cancer cells, including prostate cancer PC3 cells, to iPSCs. Most interestingly, these cells are tumor-free, forming no teratomas as human stem cells or induced pluripotent stem cells (iPSCs). In this Idea Development Award, we ask the question whether we can convert prostate cancer cells in vivo by introducing mir-302s and make cancer cells to become normal cells. If so, this approach will introduce an innovative paradigm for treating prostate cancer and challenge current concept of fighting against prostate cancer. If this approach works for prostate cancer patients, the same approach may also work for other cancer patients.

The rationale for the proposed work is based on recent observation that a type of cell in our body can be changed into a different type of cells. For example, to activate three dormant genes in the pancreatic cells that make enzymes would prompt these cells to transform themselves into cells to make insulin. The objective for the proposed work is to activate mir-302s in prostate cancer cells in vivo (in mice) and to transform these cancer cells to become normal cells. If we can successfully show the technology works in the mice, it is likely the approach will be tested in human within three to five years after the completion of this project. This approach offers great potential therapeutically because direct reprogramming represents a more straightforward strategy to treat cancers involving loss of function of specific normal cell populations so that one needs only to correct the uncontrolled cancer cells to become controlled normal cells.