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Peer-reviewedCC BY 4.0Advanced Science

CircFAM65A/CANX Condensates Sequester FAM134B to Inhibit ER‐phagy and Suppress Hepatocellular Carcinoma Progression

4 more authors
  1. 1School of Life Sciences and Technology Northwestern Polytechnical University Xi'an China
  2. 2Department of Urology Xijing Hospital Air Force Medical University Xi'an China

Abstract

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.

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BibTeX
@article{ru2026circfam65acanx,
  title = {{CircFAM65A/CANX Condensates Sequester FAM134B to Inhibit ER‐phagy and Suppress Hepatocellular Carcinoma Progression}},
  author = {Wenxiu Ru and Lunbiao Gan and Yu Lu and Yujing Guo and Qian Huang and Sha Yin and Fengze Nie and Sijia Di and Jiaqi Ning and Siyu Yao and Huanhuan Wan and Le Liu and Zehua Liu and Fa Yang and Weijun Qin and Weihong Wen},
  journal = {Advanced Science},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78469},
  url = {https://doi.org/10.1002/advs.78469},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - CircFAM65A/CANX Condensates Sequester FAM134B to Inhibit ER‐phagy and Suppress Hepatocellular Carcinoma Progression
AU  - Wenxiu Ru
AU  - Lunbiao Gan
AU  - Yu Lu
AU  - Yujing Guo
AU  - Qian Huang
AU  - Sha Yin
AU  - Fengze Nie
AU  - Sijia Di
AU  - Jiaqi Ning
AU  - Siyu Yao
AU  - Huanhuan Wan
AU  - Le Liu
AU  - Zehua Liu
AU  - Fa Yang
AU  - Weijun Qin
AU  - Weihong Wen
PY  - 2026
DA  - 2026/10/27
JO  - Advanced Science
DO  - 10.1002/advs.78469
UR  - https://doi.org/10.1002/advs.78469
AB  - 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.
SN  - 2198-3844
ER  -