Oncogenic MYC Activates a Feedforward Regulatory Loop Promoting Essential Amino Acid Metabolism and Tumorigenesis

Oncogenic MYC selectively activates Slc7a5 and Slc43a1 transcription and thus promotes essential amino acids (EAAs) uptake in Daudi cells. Elevated EAAs in turn stimulate Myc mRNA translation, prompting us to investigate whether Slc7a5/Slc43a1 inhibition affects MYC-dependent transcription. We performed microarrays to profile global gene expression and to identify Slc7a5-regulated genes. Daudi cells were infected with control shRNA, Slc7a5 shRNA or C-Myc shRNA, respectively. C-Myc shRNA-treated cells were used as a positive control.

致癌性MYC可选择性激活溶质载体家族7成员5（Slc7a5）与溶质载体家族43成员1（Slc43a1）的转录，进而促进Daudi细胞对必需氨基酸（essential amino acids, EAAs）的摄取。升高的必需氨基酸可反向刺激Myc mRNA的翻译，据此我们着手探究Slc7a5/Slc43a1的抑制是否会影响MYC依赖型转录。我们通过基因芯片（microarrays）分析全基因表达谱，以鉴定受Slc7a5调控的靶基因。将Daudi细胞分别感染对照短发夹RNA（short hairpin RNA, shRNA）、Slc7a5 shRNA或C-Myc shRNA，其中经C-Myc shRNA处理的细胞作为阳性对照。