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Induction of TRIM22 promotes autophagy and apoptosis of colorectal cancer through reactive oxygen species generation.

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Journal of translational medicine 📖 저널 OA 96.1% 2021: 1/1 OA 2022: 1/1 OA 2023: 4/4 OA 2024: 24/24 OA 2025: 173/173 OA 2026: 133/147 OA 2021~2026 2026 Vol.24(1)
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Ma X, Ruddarraju RR, Li Y, Shen B, Liu H, Ge C, Peng N, Gao L, Wang C, Zhang G, Dai F, Lv X

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[BACKGROUND] Colorectal cancer (CRC) is one of the most common causes of cancer-associated death worldwide, and a rapid increase in the incidence and mortality of CRC has been predicted with a marked

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APA Ma X, Ruddarraju RR, et al. (2026). Induction of TRIM22 promotes autophagy and apoptosis of colorectal cancer through reactive oxygen species generation.. Journal of translational medicine, 24(1). https://doi.org/10.1186/s12967-026-07839-2
MLA Ma X, et al.. "Induction of TRIM22 promotes autophagy and apoptosis of colorectal cancer through reactive oxygen species generation.." Journal of translational medicine, vol. 24, no. 1, 2026.
PMID 41668063 ↗

Abstract

[BACKGROUND] Colorectal cancer (CRC) is one of the most common causes of cancer-associated death worldwide, and a rapid increase in the incidence and mortality of CRC has been predicted with a marked trend in the younger age group. Therefore, identifying novel therapeutic targets and developing effective therapies for CRC treatment is needed. Tripartite motif 22 (TRIM22) has been implicated in several cancers; however, its role in CRC therapy remains unknown.

[METHODS] ¹H NMR, ¹³C NMR, high-resolution mass, and high performance liquid chromatography were used to determine novel pyrroloquinoline-polyamine analogues. MTT and colony formation assays were employed to detect the effects of TRIM22 and a novel pyrroloquinoline-polyamine analogue 8d on CRC. Flow cytometry was used to detect apoptosis, reactive oxygen species (ROS), and lysosomal pH. Transmission electron microscope, mCherry-GFP-LC3 plasmid, and monodansylcadaverine were utilized to examine autophagy. Cellular thermal shift assay, surface plasmon resonance, and a comprehensive computational analysis were used to investigate the interaction between TRIM22 and compound 8d. Western blotting and qRT-PCR analysis were performed to examine changes in protein and mRNA levels. Animal models were established to investigate the role of TRIM22 and compound 8d in progression of CRC.

[RESULTS] In this study, we found that TRIM22 inhibited tumor growth of CRC in vitro and in vivo, and identified a novel pyrroloquinoline-polyamine analogue, designated compound 8d, which upregulated the protein levels of TRIM22 in both CRC cells and tumor tissues. Compound 8d directly bound to TRIM22 and increased its stability. Compound 8d significantly suppressed tumor growth and pulmonary metastasis of CRC in vitro and in vivo. Genetic inhibition of TRIM22 reversed the inhibitory effects of compound 8d on CRC in vitro and in vivo. TRIM22 silencing decreased compound 8d-induced nuclear factor erythroid 2-related factor 2 downregulation and ROS-mediated autophagy and apoptosis.

[CONCLUSION] These findings highlighted the potential of compound 8d as a promising anticancer agent and targeting TRIM22 may provide a novel therapeutic approach for CRC treatment.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12967-026-07839-2.

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