Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC
Abstract Background Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to th...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-09-01
|
| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-022-00380-2 |
| _version_ | 1811273663563956224 |
|---|---|
| author | Jie-pin Li Yuan-jie Liu Shu-hong Zeng Hai-jian Gao Yu-gen Chen Xi Zou |
| author_facet | Jie-pin Li Yuan-jie Liu Shu-hong Zeng Hai-jian Gao Yu-gen Chen Xi Zou |
| author_sort | Jie-pin Li |
| collection | DOAJ |
| description | Abstract Background Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to the mitochondrial respiratory chain. Methods We investigated the potential oncogenic role of COX subunit 4 isoform 2 gene (COX4I2) in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and COX regression analysis to examine whether COX4I2 overexpression can predict colorectal cancer (CRC) prognosis. The association of COX4I2 levels with clinical features and its biological actions were evaluated both in vitro and in vivo. Results Our analysis showed that elevated COX4I2 levels were correlated with poor clinical outcomes. We also observed that that COX4I2 may be involved in epithelial-mesenchymal transition, activation of cancer-related fibroblasts and angiogenesis in relation to fibroblast growth factor 1. Conclusions The COX4I2 level may be a predictor of outcome in CRC and may represent a novel target for treatment development. Graphical Abstract |
| first_indexed | 2024-04-12T23:03:17Z |
| format | Article |
| id | doaj.art-4387d07ea61443a89e21c4e354d2100d |
| institution | Directory Open Access Journal |
| issn | 1425-8153 1689-1392 |
| language | English |
| last_indexed | 2024-04-12T23:03:17Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-4387d07ea61443a89e21c4e354d2100d2022-12-22T03:12:59ZengBMCCellular & Molecular Biology Letters1425-81531689-13922022-09-0127112310.1186/s11658-022-00380-2Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRCJie-pin Li0Yuan-jie Liu1Shu-hong Zeng2Hai-jian Gao3Yu-gen Chen4Xi Zou5Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese MedicineZhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese MedicineAbstract Background Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to the mitochondrial respiratory chain. Methods We investigated the potential oncogenic role of COX subunit 4 isoform 2 gene (COX4I2) in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and COX regression analysis to examine whether COX4I2 overexpression can predict colorectal cancer (CRC) prognosis. The association of COX4I2 levels with clinical features and its biological actions were evaluated both in vitro and in vivo. Results Our analysis showed that elevated COX4I2 levels were correlated with poor clinical outcomes. We also observed that that COX4I2 may be involved in epithelial-mesenchymal transition, activation of cancer-related fibroblasts and angiogenesis in relation to fibroblast growth factor 1. Conclusions The COX4I2 level may be a predictor of outcome in CRC and may represent a novel target for treatment development. Graphical Abstracthttps://doi.org/10.1186/s11658-022-00380-2Colorectal cancerCOX4I2Fibroblast growth factor 1Epithelial–mesenchymal transitionAngiogenesisCancer-associated fibroblasts |
| spellingShingle | Jie-pin Li Yuan-jie Liu Shu-hong Zeng Hai-jian Gao Yu-gen Chen Xi Zou Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC Cellular & Molecular Biology Letters Colorectal cancer COX4I2 Fibroblast growth factor 1 Epithelial–mesenchymal transition Angiogenesis Cancer-associated fibroblasts |
| title | Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC |
| title_full | Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC |
| title_fullStr | Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC |
| title_full_unstemmed | Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC |
| title_short | Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC |
| title_sort | identification of cox4i2 as a hypoxia associated gene acting through fgf1 to promote emt and angiogenesis in crc |
| topic | Colorectal cancer COX4I2 Fibroblast growth factor 1 Epithelial–mesenchymal transition Angiogenesis Cancer-associated fibroblasts |
| url | https://doi.org/10.1186/s11658-022-00380-2 |
| work_keys_str_mv | AT jiepinli identificationofcox4i2asahypoxiaassociatedgeneactingthroughfgf1topromoteemtandangiogenesisincrc AT yuanjieliu identificationofcox4i2asahypoxiaassociatedgeneactingthroughfgf1topromoteemtandangiogenesisincrc AT shuhongzeng identificationofcox4i2asahypoxiaassociatedgeneactingthroughfgf1topromoteemtandangiogenesisincrc AT haijiangao identificationofcox4i2asahypoxiaassociatedgeneactingthroughfgf1topromoteemtandangiogenesisincrc AT yugenchen identificationofcox4i2asahypoxiaassociatedgeneactingthroughfgf1topromoteemtandangiogenesisincrc AT xizou identificationofcox4i2asahypoxiaassociatedgeneactingthroughfgf1topromoteemtandangiogenesisincrc |