Comprehensive Proteomics Reveals Pachymic Acid Targeting RBMX via hnRNPC Degradation in Colorectal Cancer
6 affiliations
- 1School of Pharmaceutical Sciences, State Key Laboratory of Traditional Chinese Medicine Syndrome, Chinese Medicine Guangdong Laboratory (Hengqin), Guangzhou University of Chinese Medicine, Guangzhou 510006, China
- 2Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China
- 3Shenzhen Bay Laboratory, Shenzhen 518132, China
- 4State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China
- 5Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315300, China
- 6Ningbo Cixi Institute of Biomedical Engineering, Ningbo 315300, China
Abstract
Pachymic acid (PA), a major bioactive component of Poria cocos, suppresses colorectal cancer (CRC) proliferation and invasion by disrupting glycolysis. However, its antitumor activity and underlying mechanisms in vitro and in vivo remain unclear. RNA-binding proteins (RBPs) are key post-transcriptional regulators in CRC, but their mechanisms of action and therapeutic potential remain poorly understood. Here, we employed limited proteolysis-mass spectrometry (LiP-MS), a target deconvolution approach that does not require prior chemical modification, to profile changes in protein conformation within complex proteomes upon PA treatment in cells. Our findings revealed that RBMX (RNA-binding motif protein X-linked) acts as a target of PA and undergoes concentration-dependent conformational changes, as supported by binding validation and functional assays performed in vitro and in vivo. Furthermore, proximity-labeling mass spectrometry (PL-MS) analysis revealed that RBMX interacts with heterogeneous nuclear ribonucleoprotein C (hnRNPC). Functional assays demonstrated that PA treatment induces RBMX-dependent degradation of hnRNPC, thereby suppressing CRC cell proliferation and tumor growth. In summary, this study identifies RBMX as a molecular target of PA through LiP-MS, providing new insights into the mechanisms underlying PA-mediated CRC suppression and highlighting the RBMX–hnRNPC axis as an important mediator of its antitumor effects.
Related
- Comprehensive Proteomics Reveals Acute Osmoregulatory Responses in the Intestine of Oreochromis mossambicus Under Salinity, Alkalinity, and Combined Saline-Alkaline Stress.
- Towards a Comprehensive Screening Approach for Detecting Gene Doping in Racehorses and Sport Horses by Targeting Common and Intrinsic Plasmid Sequences
- Mast cell–derived SPP1 promotes colorectal cancer liver metastasis by suppressing BTG1-mediated JUN degradation
- Engineered CTLA-4 targeting chimeras for targeted protein degradation and immune synapse reprogramming
- Tubocapsenolide A Overcomes Oxaliplatin Resistance in Colorectal Cancer by Targeting PLK1 to Impair CEP55-ESCRT-Associated Vesicular Damage Clearance.
BibTeX
@article{ling2026comprehensive,
title = {{Comprehensive Proteomics Reveals Pachymic Acid Targeting RBMX via hnRNPC Degradation in Colorectal Cancer}},
author = {Weichao Ling and Meijing Song and Xinlin Li and Yu Li and Yuhao An and Zhidong Chen and Zhijun Ruan and Yang Zhou and Linlin Lu and Zigang Li and Rui Wang},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211992},
url = {https://www.mdpi.com/2073-4409/15/21/1992},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comprehensive Proteomics Reveals Pachymic Acid Targeting RBMX via hnRNPC Degradation in Colorectal Cancer
AU - Weichao Ling
AU - Meijing Song
AU - Xinlin Li
AU - Yu Li
AU - Yuhao An
AU - Zhidong Chen
AU - Zhijun Ruan
AU - Yang Zhou
AU - Linlin Lu
AU - Zigang Li
AU - Rui Wang
PY - 2026
DA - 2026/10/31
JO - Cells
DO - 10.3390/cells15211992
UR - https://www.mdpi.com/2073-4409/15/21/1992
AB - Pachymic acid (PA), a major bioactive component of Poria cocos, suppresses colorectal cancer (CRC) proliferation and invasion by disrupting glycolysis. However, its antitumor activity and underlying mechanisms in vitro and in vivo remain unclear. RNA-binding proteins (RBPs) are key post-transcriptional regulators in CRC, but their mechanisms of action and therapeutic potential remain poorly understood. Here, we employed limited proteolysis-mass spectrometry (LiP-MS), a target deconvolution approach that does not require prior chemical modification, to profile changes in protein conformation within complex proteomes upon PA treatment in cells. Our findings revealed that RBMX (RNA-binding motif protein X-linked) acts as a target of PA and undergoes concentration-dependent conformational changes, as supported by binding validation and functional assays performed in vitro and in vivo. Furthermore, proximity-labeling mass spectrometry (PL-MS) analysis revealed that RBMX interacts with heterogeneous nuclear ribonucleoprotein C (hnRNPC). Functional assays demonstrated that PA treatment induces RBMX-dependent degradation of hnRNPC, thereby suppressing CRC cell proliferation and tumor growth. In summary, this study identifies RBMX as a molecular target of PA through LiP-MS, providing new insights into the mechanisms underlying PA-mediated CRC suppression and highlighting the RBMX–hnRNPC axis as an important mediator of its antitumor effects.
SN - 2073-4409
ER -