TABLE 1.
Core clock genes and their association with breast cancer progression.
| SI No | Gene | Role in breast cancer | Breast cancer models | Citation |
|---|---|---|---|---|
| 1 | Period 2 (PER2) down regulation | Increases the levels of Cyclin D1 and Cyclin E thus doubling the mammary tumor cell proliferation | Female C3HeB/FeJ (C3H) mice and Matured T-cell lymphoma (MTCL) cells | Yang et al. (2009) |
| 2 | Knockdown of Cryptochrome (Cry2) | Adverse effect on regulation of DNA repair mechanism and genome instability | MCF-7 | Hoffman et al. (2010) |
| 3 | Per2 gene Suppression/depletion | Increased cell invasion | SKBR-3 and MDA-MB-231 | Hwang-Verslues et al. (2013) |
| 4 | Expression of 17 clock components | Worse prognosis associated with loss of clock genes | Tumors from node- negative breast cancer patients | Cadenas et al. (2014) |
| 5 | Per2 silencing | Sensitivity towards cytotoxic effects of chemotherapeutic drug | MDA-MB-231 | Mitchell and Engelbrecht, (2015) |
| 6 | ARNTL over expression | Resistance towards radiation | MCF-7 | Mandl et al. (2015) |
| 7 | 7 core clock transcription factors including Rev-Erba and Rorg | Increased oxidative stress and hepatic polyploidy | 4T1-bearing breast cancer mice | Hojo et al. (2017) |
| 8 | Circadian expression of Aldh3a1 | Circadian dynamics of the cancer stem cells are regulated by the circadian clock within the tumor microenvironment | 4T1 mouse breast cancer cells | Matsunaga et al. (2018) |
| 9 | CLOCK, BMAL1, NPAS2, PER1, PER2, PER3 and CRY1, CRY2, TIMELESS, CSNK1E | Under-expression of PER1, PER2, PER3, CRY2 and over-expression of CLOCK, TIMELESS | Breast tumor tissue and adjacent normal tissue | Lesicka et al. (2018) |
| 10 | CLOCK, BMAL1, PERIOD (PER1, 2, 3), CRYPTOCHROME (CRY1, 2), and TIMELESS | Aberrant methylation patterns in circadian rhythm genes can be used as novel biomarkers | Breast tumor tissue and adjacent normal tissue | Lesicka et al. (2019) |
| 11 | Circadian oscillations of BMAL1 and PER2 | Circadian rhythms are disrupted in high-grade tumors | MCF-7 and MDA-MB-231 | Lellupitiyage Don et al. (2019) |
| 12 | Overexpression of BMAL1 | Enhances cell invasion and metastasis | HEK-293T, MCF-7, T47D, ZR-75-30 and MDA-MB-231 cells | Wang et al. (2019) |
| 13 | Upregulation of TIMELESS (TIM) | Elevated cell proliferation and mitochondrial respiration | MCF7 and T47D | Zhang et al. (2020) |