Circadian disruption-induced microRNAome deregulation in rat mammary gland tissues

Abstract

Breast cancer is the most common malignancy affecting women worldwide, and evidence is mounting that circadian-disruption-induced breast cancer is a warranted concern. Although studies on the role of epigenetics have provided valuable insights, and although epigenetics has been increasingly recognized in the etiology of breast cancer, relatively few studies have investigated the epigenetic link between circadian disruption (CD) and breast cancer. Using a proven photoperiod-shifting paradigm, differing degrees of CD, various tissue-extraction time points, and Illumina sequencing, we investigated the effect of CD on miRNA expression in the mammary tissues of a rodent model system. To our knowledge, our results are the first to illustrate CD-induced changes in miRNA expressions in mammary tissues. Furthermore, it is likely that these miRNA expression changes exhibit varying time frames of plasticity linked to both the degree of CD and length of reentrainment, and that the expression changes are influenced by the light and dark phases of the 24-hour circadian cycle. Of the differentially expressed miRNAs identified in the present study, all but one have been linked to breast cancer, and many have predicted circadian-relevant targets that play a role in breast cancer development. Based on the analysis of protein levels in the same tissues, we also propose that the initiation and development of CD-induced breast cancer may be linked to an interconnected web of increased NF-κB activity and increased levels of Tudor-SN, STAT3, and BCL6, with aberrant CD-induced downregulation of miR-127 and miR-146b potentially contributing to this dynamic. This study provides direct evidence that CD induces changes in miRNA levels in mammary tissues with potentially malignant consequences, thus indicating that the role of miRNAs in CD-induced breast cancer should not be dismissed.

Histological and Immunohistochemical Study on the Effect of Constant Light Exposure on T Lymphocyte Subsets in the Thymus and Lymph Node of Male Albino Rats

“…Interleukin-4 (IL-4) was identified as a B cell-stimulating factor critical for class-switch [52] . Circadian disruption also would result in aberrant changes to miRNAs [53] . Micro RNA (miRNA) was found to be involved in the regulation of TFH cells.…”

“…Micro RNA (miRNA) was found to be involved in the regulation of TFH cells. Abnormal control TFH could induce autoimmune disease [53] .…”

Tudor‑staphylococcal nuclease regulates the expression and biological function of alkylglycerone phosphate synthase via nuclear factor‑κB and microRNA‑127 in human glioma U87MG cells

“…MicroRNAs (miRNAs/miRs) are an important molecular mediator of cell genetic changes, and are directly or indirectly associated with the occurrence and development of a number (6)(7)(8)(9)(10). Previous studies have indicated that Tudor-SN has a close association with lipid metabolism, and that the expression of lipoprotein in liver cells can be affected through adjustment of lipid metabolism-associated genes (11,12).…”

Entrainment of Breast Cell Lines Results in Rhythmic Fluctuations of MicroRNAs

“…Thus, miRNAs seem to be a potential way in which to investigate biological timing processes that might be critical for cancer cells [ 18 , 19 ]. A recent study provides direct evidence that circadian disruption induces changes in miRNA levels in the mammary tissue of rats, which may lead to malignant consequences [ 20 ].…”