LncRNA MIR4435-2HG targets desmoplakin and promotes growth and metastasis of gastric cancer by activating Wnt/β-catenin signaling

作者：Haiyong Wang, Mengjie Wu, Yimin Lu, Kuifeng He, Xiaolu Cai, Xiongfei Yu, Jun Lü, Lisong Teng · 发表于：Aging · 年份：2019 · DOI：10.18632/aging.102164 · 被引用次数：87 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、Cholangiocarcinoma and Gallbladder Cancer Studies

, as well as tumorigenicity in mice. Using RNA pull-down and mass-spectrometry analyses we found and verified a direct and novel interaction between MIR4435-2HG and desmoplakin (DSP), the most abundant desmosomal protein. Overexpression and knockdown experiments revealed opposing roles for DSP and MIR4435-2HG, unmasking a cascade through which MIR4435-2HG binds to and inhibits DSP, leading to activation of WNT/β-catenin signaling and epithelial-mesenchymal transition in gastric cancer cells. We propose that the MIR4435-2HG/DSP/WNT axis serves as a critical effector of carcinogenesis and progression of gastric cancer, and could be exploited therapeutically to improve patients' outcomes.