Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer
Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-01-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10119 |
| _version_ | 1797261363219791872 |
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| author | Cui Tang Aili Wang YanLin Zhao WenYing Mou Jun Jiang Jie Kuang Bin Sun Erjiang Tang |
| author_facet | Cui Tang Aili Wang YanLin Zhao WenYing Mou Jun Jiang Jie Kuang Bin Sun Erjiang Tang |
| author_sort | Cui Tang |
| collection | DOAJ |
| description |
Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention.
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| first_indexed | 2024-04-24T23:40:01Z |
| format | Article |
| id | doaj.art-51dece0fe06349f5bc61aa31572f4508 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:40:01Z |
| publishDate | 2024-01-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-51dece0fe06349f5bc61aa31572f45082024-03-15T13:20:54ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-01-0110.17305/bb.2024.10119Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancerCui Tang0https://orcid.org/0000-0002-7018-5763Aili Wang1YanLin Zhao2https://orcid.org/0000-0002-2089-8028WenYing Mou3Jun Jiang4https://orcid.org/0009-0000-3404-2071Jie Kuang5Bin Sun6https://orcid.org/0000-0002-5082-3326Erjiang Tang7Department of Radiology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaCenter for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Radiology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Radiology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaEndoscopy Center, Minhang District Central Hospital of Fudan University, Shanghai, ChinaDepartment of Radiology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaCenter for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaCenter for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University Colorectal cancer (CRC) presents a landscape of intricate molecular dynamics. In this study, we focused on the role of the leukotriene B4 receptor (LTB4R) in CRC, exploring its significance in the disease's progression and potential therapeutic approaches. Using bioinformatics analysis of the GSE164191 and the Cancer Genome Atlas-colorectal adenocarcinoma (TCGA-COAD) datasets, we identified LTB4R as a hub gene influencing CRC prognosis. Subsequently, we examined the relationship between LTB4R expression, apoptosis, and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway through cellular and mice experiments. Our findings revealed that LTB4R is highly expressed in CRC samples and is pivotal for determining prognosis. In vitro experiments demonstrated that silencing LTB4R significantly impeded CRC cell viability, migration, invasion, and colony formation. Correspondingly, in vivo tests indicated that LTB4R knockdown led to markedly slower tumor growth in mice models. Further in-depth investigation revealed that LTB4R knockdown significantly amplified the apoptosis in CRC cells and upregulated the expression of apoptosis-related proteins, such as caspase-3 and caspase-9, while diminishing p53 expression. Interestingly, silencing LTB4R also resulted in a significant downregulation of the PI3K/AKT/mTOR signaling pathway. Moreover, pretreatment with the PI3K activator 740Y-P only partially attenuated the effects of LTB4R knockdown on CRC cell behavior, emphasizing LTB4R's dominant influence in CRC cell dynamics and signaling pathways. LTB4R stands out as a critical factor in CRC progression, profoundly affecting cellular behavior, apoptotic responses, and the PI3K/AKT/mTOR signaling pathway. These findings not only shed light on LTB4R's role in CRC but also establish it as a potential diagnostic biomarker and a promising target for therapeutic intervention. https://www.bjbms.org/ojs/index.php/bjbms/article/view/10119Leukotriene B4 receptor (LTB4R)colorectal cancer (CRC)phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathwayapoptosis |
| spellingShingle | Cui Tang Aili Wang YanLin Zhao WenYing Mou Jun Jiang Jie Kuang Bin Sun Erjiang Tang Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer Biomolecules & Biomedicine Leukotriene B4 receptor (LTB4R) colorectal cancer (CRC) phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway apoptosis |
| title | Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer |
| title_full | Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer |
| title_fullStr | Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer |
| title_full_unstemmed | Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer |
| title_short | Leukotriene B4 receptor knockdown affects PI3K/AKT/mTOR signaling and apoptotic responses in colorectal cancer |
| title_sort | leukotriene b4 receptor knockdown affects pi3k akt mtor signaling and apoptotic responses in colorectal cancer |
| topic | Leukotriene B4 receptor (LTB4R) colorectal cancer (CRC) phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway apoptosis |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10119 |
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