CircFAM65A/CANX Condensates Sequester FAM134B to Inhibit ER‐phagy and Suppress Hepatocellular Carcinoma Progression
Wenxiu Ru, Lunbiao Gan, Yu Lu, Yujing Guo, Qian Huang, Sha Yin, Fengze Nie, Sijia Di, Jiaqi Ning, Siyu Yao, Huanhuan Wan, Le Liu, Zehua Liu, Fa Yang, Weijun Qin, Weihong WenABSTRACT
ER‐phagy has been implicated in tumor progression; however, its regulatory mechanisms in hepatocellular carcinoma (HCC) remain largely unexplored. Here, we identified circFAM65A as a novel circRNA that is downregulated in HCC and its overexpression suppressed HCC progression. Mechanistically, circFAM65A interacted with CANX and attenuated the CANX‐mediated promotion of ER‐phagy and HCC progression. Specifically, circFAM65A promoted CANX condensate formation, and these condensates sequestered FAM134B, reducing the FAM134B‐LC3 interaction and suppressing ER‐phagy. Furthermore, a biomimetic membrane‐coated nanoparticle (PLGA/circFAM65A@M‐3E11) was designed to deliver circFAM65A, which effectively inhibited HCC growth in vivo. Together, these findings identify circFAM65A as a regulator of CANX‐mediated ER‐phagy and support its delivery as a potential therapeutic strategy for HCC.