2. Academic Validation
  3. miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy

miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy

  • Sci Rep. 2024 Oct 16;14(1):24284. doi: 10.1038/s41598-024-75746-x.
Yi Fang 1 2 3,  Yulun Wu 1 2,  Xinran Zhang 1 2,  Lihui Wei 1 2 3,  Liya Liu 1 4,  Youqin Chen 5,  Daxin Chen 1 2 3,  Nanhui Xu 1 2,  Liujin Cao 1 2,  Jie Zhu 6,  Mian Chen 6,  Ying Cheng 1 2,  Thomas J Sferra 5,  Mengying Yao 1 2,  Aling Shen 7 8 9,  Jun Peng 10 11 12
Affiliations

Affiliations

  • 1 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
  • 2 Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
  • 3 Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
  • 4 Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
  • 5 Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, 44106, USA.
  • 6 School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
  • 7 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China. 2018025@fjtcm.edu.cn.
  • 8 Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China. 2018025@fjtcm.edu.cn.
  • 9 Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China. 2018025@fjtcm.edu.cn.
  • 10 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China. pjunlab@hotmail.com.
  • 11 Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China. pjunlab@hotmail.com.
  • 12 Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China. pjunlab@hotmail.com.
PMID: 39414903 DOI: 10.1038/s41598-024-75746-x
Abstract

Proteasome inhibition emerges as a promising strategy for Cancer prevention. PNO1, pivotal for colorectal Cancer (CRC) progression, is involved in Proteasome assembly in Saccharomyces cerevisiae. Hence, we aimed to explore the role of PNO1 in Proteasome assembly and its up- and down-streams in CRC. Here, we demonstrated that PNO1 knockdown suppressed CRC cells growth, Proteasome activities and assembly, as well as CDKN1B/p27Kip1 (p27) degradation. Moreover, p27 knockdown partially attenuated the inhibition of HCT116 cells growth by PNO1 knockdown. The up-stream studies of PNO1 identified miR-326 as a candidate miRNA directly targeting to CDS-region of PNO1 and its overexpression significantly down-regulated PNO1 protein expression, resulting in suppression of cell growth, decrease of Proteasome activities and assembly, as well as increasing the stability of p27 in CRC cells. These findings indicated that miR-326 overexpression can suppress CRC cell growth, acting as an endogenous Proteasome Inhibitor by targeting PNO1.

Keywords

Colorectal cancer; MiR-326; P27KIP1; PNO1; Proteasome assembly.

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