EZH2-mediated epigenetic suppression of SH3BGRL potently inhibits lung cancer progression.

Lung cancer is the leading cause of cancer-related deaths worldwide. Lung cancer stem cells (CSCs) are a small population of cancer cells with self-renewal, therapeutic resistance, and tumor relapse capability. Yet the molecular mechanisms underlying lung CSCs self-renewal remain largely unknown. Here, we report that SH3BGRL were down-regulated in lung cancer tissues comparing with normal lung tissues and SH3BGRL low expression was correlated with the poor clinical outcomes of patients with lung cancer. Moreover, SH3BGRL was also weakly expressed in lung CSCs compared with its corresponding lung cancer cells. We first characterize that EZH2 directly binds to SH3BGRL promoter and transcriptional represses SH3BGRL expression in epigenetic level. Functionally, overexpression of SH3BGRL potently suppresses Lung CSCs self-renewal in vitro. The gain of function study reveals that SH3BGRL acts as a novel tumor suppressor via inhibiting lung cancer cell proliferation and migration as well as Lung CSCs self-renewal in vitro. Collectively, our work demonstrates that SH3BGRL hold potential as a favorable prognostic marker and therapeutic target for patients with lung cancer in future.