Table 3.
Oxysterol-circadian factors influencing CRC development.
| Factor | Notes | Proposed function | References |
|---|---|---|---|
| Total serum cholesterol | Increased in humans | Higher risk for CRC | (145, 146) |
| CYP7A1 | SNP and haplotype | Associated with CRC | (147–150) |
| Oxyphytosterols | Treatment of CRC cell lines | Anti-proliferative, pro-apoptotic | (151) |
| Dietary oxysterols | Treatment of Caco-2 | Pro-apoptotic | (152) |
| 27-hydroxy cholesterol | Treatment of CRC cell lines | Anti-proliferative | (153) |
| 7α- and 7β-hydroxycholesterol, 5α,6α-epoxycholesterol, and 7β-hydroxysitosterol | Treatment of Caco-2 | Pro-apoptotic | (154–156) |
| 7β-hydroxycholesterol | Treatment of Caco-2 | Induced expression of inflammatory and chemotactic cytokines | (157) |
| 7-ketocholesterol | Treatment of Caco-2 | Reduced barrier functions, anti-apoptotic, induced viability, lower inflammatory response | (158, 159) |
| Treatment of HT-29 | Induction of ER stress | (160) | |
| Treatment of Caco-2 | Mitochondrial functionality | (161) | |
| 25-hydroxycholesterol | Treatment of Caco-2 | Reduced barrier functions, anti-apoptotic, and induced viability | (158) |
| Treatment of DLD-1 | Induction of cell death, anoikis | (162) | |
| Treatment of Caco-2 | Enhanced IL1B induction of IL8 | (163) | |
| LXR | Induction by agonist in CRC cell lines | Anti-proliferative | (164) |
| CYP8B1, CYP46A1, CYP2R1 | Higher expression in CRC | Poor prognosis | (165) |
| CYP7B1 | Higher expression in CRC | Good prognosis | (165) |
| OSBPL9 | Downregulation in CRC tumors | Poor prognosis | (166) |
| LXR | Increased expression | Good prognosis | (167) |
| Activation in HT-92 | Anti-proliferative | (168, 169) | |
| FXR | Decreased expression in CRC tumors | Poor prognosis | (170–175) |
| Knockout in mice | Increased susceptibility to chemically-induced | (171, 176) | |
| Overexpression in CRC cell lines | Reduced tumor growth, anti-proliferative, pro-apoptotic | (92, 171, 175–177) | |
| PER1, PER3 | Decreased expression in CRC tumors | Poor prognosis | (178) |
| PER1, BMAL1 | Decreased PER1 and increased BMAL1 in CRC tumors | Poor prognosis | (179) |
| PER2 | Increased in CRC tumors | Good prognosis | (178) |
| RORA | SNPs | Risk of development of CRC | (180) |
| Lower expression in CRC tumors | Good prognosis | (180) | |
| SIRT1 | Transgenic mice and human tumor specimens | Suppression of in vivo tumor formation | (181) |