Evaluating the associations between human circadian rhythms and dysregulated genes in liver cancer cells

Abstract

Network analysis is a useful approach in cancer biology as it provides information regarding the genes and proteins. In our previous study, a network analysis was performed on dysregulated genes in HepG2 cells, a hepatoblastoma cell line that lacks the viral infection, compared with normal hepatocytes, identifying the presence of 26 HUB genes. The present study aimed to identify whether these previously identified HUB genes participate in the network that controls the human circadian rhythms. The results of the present study demonstrated that 20/26 HUB genes were associated with the metabolic processes that control human circadian rhythms, which supports the hypothesis that a number of cancer types are dependent from circadian cycles. In addition, it was revealed that the CLOCK circadian regulator gene was associated, via cytoskeleton associated protein 5 (CKAP5), with the HUB genes of the HepG2 network, and that CKAP5 was associated with three other circadian genes (casein kinase 1ε, casein kinase 1δ and histone deacetylase 4) and 10 HepG2 genes (SH2 domain containing, ZW10 interacting kinetochore protein, aurora kinase B, cell division cycle 20, centromere protein A, inner centromere protein, mitotic arrest deficient 2 like 1, baculoviral IAP repeat containing 5, SPC24 NDC80 kinetochore complex component and kinesin family member 2C). Furthermore, the genes that associate the circadian system with liver cancer were demonstrated to encode intrinsically disordered proteins. Finally, the results of the present study identified the microRNAs involved in the network formed by the overlapping of HepG2 and circadian genes.

Identification and meta‑analysis of copy number variation‑driven circadian clock genes for colorectal cancer

“…Research by the International Agency for Research on Cancer has also demonstrated that this disruption increases the risk of CRC (7). Several previous studies have also demonstrated that large variations in expression levels, both up- and downregulated, and the circadian clock genes are associated with tumor progression and mammalian tumorigenesis for several malignancies, such as breast cancer (8), liver cancer (9) and colorectal carcinoma (10). In addition, the association between single nucleotide polymorphisms (SNPs) in circadian clock genes and disease has also been analyzed (11,12).…”

New Insights Into the Circadian Rhythm and Its Related Diseases

“…A large quantity of studies have suggested that circadian disruptions are closely associated with the formation and development of various diseases including cancer (Momma et al, 2017; Polo et al, 2017; Xiong et al, 2018), dysplasia (Vilches et al, 2014; Voiculescu et al, 2016; Zhao et al, 2018; Zhou et al, 2018), cardiovascular disease (Angelousi et al, 2018), obesity (Antunes et al, 2010), diabetes (Pan et al, 2011), and sleep disorder (Logan and McClung, 2019). As previously described, the cell cycle and the circadian clock are two basic periodic processes of a day, and they are interrelated.…”

The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

“…Simultaneously, CKAP5 was associated with three circadianrelated genes (CSNK1E, CSNK1D, and HDAC4). Furthermore, it was found that miR-195-5p, miR-192-5p, miR-122-5p, and miR-101-3p were involved in the dysregulation of circadian genes which led to HCC [76]. A series of miR-NAs targeting circadian genes have been identified using ENCORI (http://starbase.sysu.edu.cn/) [77].…”