Lung Cancer

My second project is to identify the KMT2C deficient promote small cell lung cancer (SCLC) metastasis through regulating epigenetics reprogramming. I’m in charge of all omics analysis in this project. Firstly, I find the KMT2C is significantly down-regulated in metastasis SCLC cells on scRNA-seq data from multiple cohorts, and SCLC patents with KMT2C mutation are almost in extensive stage, which provides solid evidences to test the function of KMT2C in SCLC metastasis. Then, I identify the DNMT3A is the direct downstream target of KMT2C in SCLC with CUT&Tag-seq data including anti-KMT2C data and multiple histone modification data, which reveals the KMT2C deficient can lead an epigenetics reprogramming through coherently regulating the histone-DNA modification. With the help of lab members, we have validated the regulation mechanism in vitro and in vivo. Besides, we find S-(5′-adenosyl)-l-methionine, the common cofactor of histone and DNA methyltransferases, could be a candidate drug to inhibit the SCLC metastasis. Overall, the experience of SCLC study makes me skillful and even stimulate my curios about epigenetics reprogramming in cancer.