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Quantitative Proteomics Analysis of Berberine-Treated Colon Cancer Cells Reveals Potential Therapy Targets
Pengfei Li1, Zhifang Hao1, Huanhuan Liu1
1College of Life Sciences, Northwest University, Xi'an 710069, China.
Abstract:
Colon cancer is one of the most lethal malignancies worldwide. Berberine has been found to exert potential anti-colon cancer activity in vitro and in vivo, although the detailed regulatory mechanism is still unclear. This study aims to identify the underlying crucial proteins and regulatory networks associated with berberine treatment of colon cancer by using proteomics as well as publicly available transcriptomics and tissue array data. Proteome profiling of berberine-treated colon cancer cells demonstrated that among 5130 identified proteins, the expression of 865 and 675 proteins were changed in berberine-treated HCT116 and DLD1 cells, respectively. Moreover, 54 differently expressed proteins that overlapped in both cell lines were mainly involved in mitochondrial protein synthesis, calcium mobilization, and metabolism of fat-soluble vitamins. Finally, GTPase ERAL1 and mitochondrial ribosomal proteins including MRPL11, 15, 30, 37, 40, and 52 were identified as hub proteins of berberine-treated colon cancer cells. These proteins have higher transcriptional and translational levels in colon tumor samples than that of colon normal samples, and were significantly down-regulated in berberine-treated colon cancer cells. Genetic dependency analysis showed that silencing the gene expression of seven hub proteins could inhibit the proliferation of colon cancer cells. This study sheds a light for elucidating the berberine-related regulatory signaling pathways in colon cancer, and suggests that ERAL1 and several mitochondrial ribosomal proteins might be promising therapeutic targets for colon cancer.
Insights
Berberine shows potential against colon cancer by down-regulating key mitochondrial proteins like ERAL1 and MRPLs. These proteins, crucial for cancer cell growth, represent potential new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Colon cancer is a leading cause of cancer mortality globally.
- Berberine exhibits potential anti-colon cancer effects, but its precise mechanism remains elusive.
- Identifying key molecular targets is crucial for developing effective colon cancer therapies.
Purpose of the Study:
- To elucidate the protein expression changes and regulatory networks influenced by berberine in colon cancer.
- To identify novel therapeutic targets for colon cancer treatment based on berberine's mechanism of action.
Main Methods:
- Proteomic profiling of berberine-treated colon cancer cell lines (HCT116 and DLD1).
- Analysis of publicly available transcriptomics and tissue array data.
- Identification of differentially expressed proteins, hub proteins, and their functional pathways.
- Genetic dependency analysis to assess the impact of hub protein silencing on cancer cell proliferation.
Main Results:
- Proteome profiling revealed significant changes in protein expression in response to berberine treatment in both cell lines.
- Fifty-four overlapping differentially expressed proteins were identified, primarily involved in mitochondrial protein synthesis, calcium mobilization, and fat-soluble vitamin metabolism.
- GTPase ERAL1 and several mitochondrial ribosomal proteins (MRPLs) were identified as key hub proteins, showing higher expression in tumors and down-regulation with berberine treatment.
- Silencing of seven identified hub protein genes significantly inhibited colon cancer cell proliferation.
Conclusions:
- Berberine treatment down-regulates specific mitochondrial proteins, including ERAL1 and MRPLs, in colon cancer cells.
- These identified hub proteins are upregulated in colon tumors and are critical for cancer cell proliferation.
- ERAL1 and mitochondrial ribosomal proteins represent promising therapeutic targets for colon cancer treatment.
