Dr. Rotem Karni and PhD student Vered Ben Hur at the Institute for Medical Research Israel-Canada of the Hebrew University,
In normal cell reproduction, a process of RNA splicing takes place. RNA (ribonucleic acid) is a family of large biological molecules that performs multiple, vital roles in the coding, decoding, regulation and expression of genes. Cellular organisms use messenger RNA, called mRNA, to convey genetic information that directs synthesis of specific proteins.
RNA splicing is similar to the process of editing a movie. In this process, the information needed for the production of a mature protein is encoded in segments called exons (which like important movie scenes are needed in a specific sequence in order to understand the movie). In the splicing process, the non-coding segments of the RNA (unimportant scenes, called introns) are spliced from the pre-mRNA and the exons are joined together.
Alternative splicing is when a specific ”scene” (or exon) is either inserted or deleted from the movie (mRNA), thus changing its meaning. Over 90 percent of the genes in our genome undergo alternative splicing of one or more of their exons, and the resulting changes in the proteins encoded by these different mRNAs are required for normal function. In cancer, the normal
process of alternative splicing is altered, and ”bad” protein forms are generated that aid cancer cell proliferation and survival.
In a study published in the online edition of Cell Reports, conducted by Ph.D. student Vered Ben Hur in the lab of Dr. Rotem Karni at the Institute for Medical Research Israel-Canada of the Hebrew University, the researchers found that breast cancer cells change the alternative splicing of an important enzyme, called S6K1, which is a protein involved in the transmission of information into the cell.
The researchers found that when this happens, breast cancer cells start to produce shorter versions of this enzyme and that these shorter versions transmit signals ordering the cells to grow, proliferate, survive and invade other tissues. On the other hand, the researchers found that the long form of this protein acts as a tumor suppressor that protects normal cells from becoming cancerous.
There are several medical implications emanating from the research, say the researchers. One of them is the use of the newly discovered short forms of S6K1 as a diagnostic marker for the detection of breast cancer. Several new anticancer drugs, which have entered the clinic recently, can inhibit the cancerous activity of the short forms of S6K1. Thus, the detection of these new forms can predict the efficacy of these drugs to treat cancer patients.
These implications were recently submitted as a patent application by Yissum, the technology transfer company of the Hebrew University. Another future application will be to ”reverse” the alternative splicing of S6K1 in cancer cells back to the normal situation as a novel anti-cancer therapy. The research group of Dr. Karni is actively engaged in this effort.
The Hebrew University of Jerusalem