Regulation of Hippo-YAP signaling by insulin-like growth factor-1 receptor in the tumorigenesis of diffuse large B-cell lymphoma

• DOI: 10.1186/s13045-020-00906-1
• Publication Date: 2020-06-16T12:02:36Z
• Authors: Xiangxiang Zhou; Na Chen; Hongzhi Xu; Xiaoming Zhou; Jianhong Wang; Xiaosheng Fang; Ya Zhang; Ying Li; Juan Yang; Xin Wang
• Keywords: Hippo signaling pathway

Abstract Background Hippo-Yes-associated protein (YAP) signaling is a key regulator of organ size and tumorigenesis, yet the underlying molecular mechanism still poorly understood. At present, significance Hippo-YAP pathway in diffuse large B-cell lymphoma (DLBCL) ill-defined. Methods The expression YAP DLBCL was determined public database clinical specimens. effects knockdown, CRISPR/Cas9-mediated deletion, inhibitor treatment on cell proliferation cycle were evaluated both vitro vivo. RNA sequencing conducted to detect dysregulated RNAs YAP-knockout cells. regulatory insulin-like growth factor-1 receptor (IGF-1R) explored by targeted inhibition rescue experiments. Results High significantly correlated with disease progression poor prognosis. Knockdown suppressed induced arrest Verteporfin (VP), benzoporphyrin derivative, exerted an anti-tumor effect regulating downstream target genes, CTGF CYR61. In vivo studies revealed that deletion CRISPR/Cas9 genome editing system restrained tumor growth. Moreover, downregulation IGF-1R led remarkable decrease expression. contrast, exposure IGF-1 promoted reversed inhibitors. Conclusions Our study highlights critical role pathogenesis uncovers signaling, suggesting novel therapeutic strategy for DLBCL.