Next Generation Sequencing Facilitates Analysis of Fangchinoline Treatment and Control SamplesTranscriptomes

Conjunctival melanoma (CM) is a rare and potentially deadly ocular tumor with poor prognosis. Thus, effective drugs to kill CM are urgently needed. Herein, we reported the discovery of a novel potential therapeutic target for CM. Through phenotypic screening of our in-house library, fangchinoline was discovered to potently inhibit the growth of CM cell lines including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that fangchinoline could suppress homologous recombination (HR)-directed DNA repair through binding to far upstream element binding protein 2 (FUBP2) and downregulating expression of the HR factors BRCA1 and RAD51. In vitro and in vivo antitumor experiments revealed that fangchinoline increased the efficacy of cisplatin by blocking HR factors and diminished the drug dose and toxicity. In summary, our work provides a promising therapeutic strategy for the treatment of CM that is worthy of extensive preclinical investigation. Examination of fangchinoline treatment and control samples in CM-AS16 cells by RNA-seq, in triplicate.