Association of Lin28 Expression and Tumorigenesis in Human Wilms’ Tumor Cell Lines

Abstract

LIN28 is an evolutionarily conserved RNA binding protein that plays an essential role in regulating developmental timing in Caenorhabditis elegans. Recently, many reports have shown the effect of LIN28 in stem cell function, cell differentiation, cell proliferation and tumorigenesis. In mammals, LIN28 is highly expressed in embryonic stem cells and in early embryogenesis. One of the major targets of LIN28 is the Let7 microRNA family. By binding to the pri/pre Let‐7 microRNA genes, LIN28 prevents the maturation of this miRNA family and thus enables the translation of genes that are suppressed by Let‐7 miRNAs. Therefore, LIN28 is capable of regulating translation and stability of oncogenes including K‐Ras, C‐Mys and many others. In cancer cells, LIN28 is up‐regulated as an oncogene, which promotes transformation and tumor progression. It has been shown by our lab that ~15% of human cancers are linked to the expression of LIN28A or its paralog LIN28B. In addition, some reports show that knocking‐down LIN28A reduces cancer cell viability and cell growth in vitro. We have shown that LIN28B is expressed in samples of Wilms’ tumor cells. In Wilms’ tumor cell lines, in vitro LIN28B‐knockdown significantly decreased cell proliferation compared with control cells. Taken together, LIN28B might function in controlling cell survival and differentiation in Wilms’ tumor. To further study the role of LIN28 in Wilms tumor formation, we will transplant “normal” and knock‐down human Wilms’ tumor cell lines under the kidney capsule of immunodeficient mice and compare. We will also over‐express LIN28A/B during normal mouse kidney development.