Poster Presentation 11th International Symposium on Autophagy 2025

Rubicon promotes hepatocellular carcinoma via suppressing selective removal of cell cycle regulators (#220)

Hitomi Imoto 1 2 3 4 , Sadatsugu Sakane 5 , Tatsuya Shioda 6 , Tatsuya Kaminishi 3 , Tetsuta Matsui 3 , Satoshi Minami 3 , Kenji Fukumoto 5 , Yoshinobu Saito 5 , Katsuhiko Sato 5 , Shu Aoyama 7 , Shogo Kobayashi 7 , Hirofumi Akita 7 , Rumiko Otsuka 2 , Akiko Kuma 3 , Hidetoshi Eguchi 7 , Hidetaka Kosako 8 , Michiaki Hamada 6 , Yumi Konagaya 9 , Hayato Hikita 5 , Tetsuo Takehara 5 , Tamotsu Yoshimori 4 , Shuhei Nakamura 1 2
  1. Department of Biochemistry, Nara Medical University, Kashihara, Nara, Japan
  2. Center for Autophagy and Anti-Aging Research, Nara Medical University, Kashihara, Nara, Japan
  3. Department of Genetics, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan
  4. Department of Beyond Cell Reborn Research, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan
  5. Department of Gastroenterology and Hepatology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan
  6. Department of Electrical Engineering and Bioscience, Waseda University, Shinjyuku-ku, Tokyo, Japan
  7. Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan
  8. Division of Cell Signaling, Tokushima University, Tokushima, Japan
  9. Laboratory for Quantitative Biology of Cell Fate Decision, RIKEN, Kobe, Hyogo, Japan

Autophagic impairment is associated with the onset of age-related disease and it plays a role in cancer, although its effects are complicated since they are context-dependent. Since Rubicon, a suppressor of autophagy, increases in the liver of aged mice, and promotes the phenotypes of high fat diet-triggered metabolic dysfunction-associated steatotic liver disease (MASLD), we investigated the role of Rubicon in hepatocellular carcinoma (HCC). We found that knockdown of Rubicon delays proliferation and invasion of hepatocellular carcinoma cells. Mechanistically, decline of Rubicon induces cell cycle arrest at the specific stage by the selective removal of several cell cycle regulators. Furthermore, we found that hepatocyte-specific Rubicon knockout mice show the decrease of tumor size and burden in diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced liver tumorigenesis. In addition, transcription of Rubicon is upregulated in HCC patients. These data indicate that Rubicon promotes hepatocellular carcinoma via suppressing targeted removal of cell cycle regulators.