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Discovery and Characterization of Functional Breast Cancer Microproteins


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1) We were able to show that loss of TINCR microprotein (TINCR-MP) regulates cell growth and are now screening throughseveral breast cancer cells to determine those lines that are most sensitive to this gene. 2) We decoupled TINCR-MPbiological activity from that of the TINCR mRNA. The TINCR mRNA regulates keratinocyte differentiation while themicroprotein does not; however, as we demonstrated in the first finding, the TINCRP-MP has unique activity on cell growth andproliferation. 3) We determined the pathways regulated by TINCR-MP using unbiased RNA-Seq and discovered that TINCRMPis a potent regulator of genes linked to injury and wound healing pathways. As cancer is commonly referred to as thewound that doesnt heal, this connection will help us pinpoint the particular genes under the influence of TINCR-MP thatregulate breast cancer cell growth and proliferation. 4) We have completed data collection for smORFs in HCC1954, MCF-7,and MD-MB-231 breast cancer cell lines. We are already preparing HCC1954, MCF-7, and MD-MB-231 cells with stablyexpressed Cas9 and have designed and ordered guide RNAs for our screens. We will complete the proposed studies by theend of the funding period and are planning to publish this work next year.



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