IGF2BP1 over-expression in skin squamous cell carcinoma cells is essential for cell growth

Highlights: • IGF2BP1 is upregulated in human skin squamous cell carcinoma (SCC) cells and tissues • IGF2BP1 shRNA or CRISPR/Cas9 knockout decreases levels of IGF2BP1-stablized mRNAs • IGF2BP1 shRNA or knockout inhibits human skin SCC cell survival and proliferation • Lnc-RNA THOR siRNA inhibits A431 cell survival and proliferation • IGF2BP1 silencing or knockout inhibits A431 xenograft growth in SCID mice The present study examined expression and potential functions of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in human skin squamous cell carcinoma (SCC). We show that IGF2BP1 mRNA and protein expression levels were upregulated in established (A431 line) and primary human skin SCC cells. Its expression was also increased in human skin SCC tissues, as compared to the normal skin tissues. In skin SCC cells, IGF2BP1 silencing or CRISPR/Cas9 knockout decreased levels of IGF2BP1-stablized mRNAs, including IGF2, CD44, Gli1 and Myc. Furthermore, skin SCC cell survival and proliferation were inhibited by IGF2BP1 silencing/knockout. Conversely, forced over-expression of IGF2BP1 further promoted A431 cell survival and proliferation. Furthermore, siRNA-mediated knockdown of IGF2BP1-bound long non-coding RNA THOR ("Lnc-THOR") similarly depleted IGF2BP1-dependent mRNAs, causing inhibition on A431 cell survival and proliferation. In vivo, IGF2BP1 silencing or knockout inhibited A431 tumor xenograft growth in mice. Together, we conclude that IGF2BP1 over-expression in skin SCC cells is essential for cell growth.