MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway
Colorectal cancer (CRC) is one of the most lethal cancers. Single-cell RNA sequencing (scRNA-seq) and protein-protein interactions (PPIs) have enabled the systematic study of CRC. In our research, the activation of the AKT pathway in CRC was analyzed by KEGG using single-cell sequencing data from the GSE144735 dataset. The correlation and PPIs of MDFI and ITGB4/LAMB3 were examined. The results were verified in the TCGA and CCLE and further tested by coimmunoprecipitation experiments. The effect of MDFI on the AKT pathway via ITGB4/LAMB3 was validated by knockdown and lentiviral overexpression experiments. The effect of MDFI on oxaliplatin/fluorouracil sensitivity was probed by colony formation assay and CCK8 assay. We discovered that MDFI was positively associated with ITGB4/LAMB3. In addition, MDFI was negatively associated with oxaliplatin/fluorouracil sensitivity. MDFI upregulated the AKT pathway by directly interacting with LAMB3 and ITGB4 in CRC cells, and enhanced the proliferation of CRC cells via the AKT pathway. Finally, MDFI reduced the sensitivity of CRC cells to oxaliplatin and fluorouracil. In conclusion, MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells, partially through the activation of the AKT signaling pathway by the binding to ITGB4/LAMB3. Our findings provide a possible molecular target for CRC therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Cancer biology & therapy - 25(2024), 1 vom: 31. März, Seite 2314324 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Ding [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.02.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/15384047.2024.2314324 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368658759 |
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| 100 | 1 | |a Ma, Ding |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 21.02.2024 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Colorectal cancer (CRC) is one of the most lethal cancers. Single-cell RNA sequencing (scRNA-seq) and protein-protein interactions (PPIs) have enabled the systematic study of CRC. In our research, the activation of the AKT pathway in CRC was analyzed by KEGG using single-cell sequencing data from the GSE144735 dataset. The correlation and PPIs of MDFI and ITGB4/LAMB3 were examined. The results were verified in the TCGA and CCLE and further tested by coimmunoprecipitation experiments. The effect of MDFI on the AKT pathway via ITGB4/LAMB3 was validated by knockdown and lentiviral overexpression experiments. The effect of MDFI on oxaliplatin/fluorouracil sensitivity was probed by colony formation assay and CCK8 assay. We discovered that MDFI was positively associated with ITGB4/LAMB3. In addition, MDFI was negatively associated with oxaliplatin/fluorouracil sensitivity. MDFI upregulated the AKT pathway by directly interacting with LAMB3 and ITGB4 in CRC cells, and enhanced the proliferation of CRC cells via the AKT pathway. Finally, MDFI reduced the sensitivity of CRC cells to oxaliplatin and fluorouracil. In conclusion, MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells, partially through the activation of the AKT signaling pathway by the binding to ITGB4/LAMB3. Our findings provide a possible molecular target for CRC therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AKT | |
| 650 | 4 | |a ITGB4/LAMB3 | |
| 650 | 4 | |a MDFI (MyoD family inhibitor) | |
| 650 | 4 | |a PPIs (protein-protein interactions) | |
| 650 | 4 | |a scRNA-seq (single-cell RNA sequencing) | |
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| 650 | 7 | |a U3P01618RT |2 NLM | |
| 650 | 7 | |a Integrin beta4 |2 NLM | |
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| 650 | 7 | |a MDFI protein, human |2 NLM | |
| 650 | 7 | |a 183511-66-2 |2 NLM | |
| 650 | 7 | |a Myogenic Regulatory Factors |2 NLM | |
| 650 | 7 | |a Oxaliplatin |2 NLM | |
| 650 | 7 | |a 04ZR38536J |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a LAMB3 protein, human |2 NLM | |
| 650 | 7 | |a Kalinin |2 NLM | |
| 700 | 1 | |a Liu, Shuwen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Kua |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Lingkai |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Lingjun |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Qilei |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Chunping |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Junhua |e verfasserin |4 aut | |
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