Evaluation The Correlation between Bmal1 and Clock Genes Expression with miRNA In kids With Bipolar Disorder
Abstract:
The study aimed to explore the influence of methylation levels of two
clock genes, Bmal1 and Clock, and the association between gene expression and
miRNA molecules (miRNA155 and miRNA211) in bipolar disorder. The study sample contains
40 kids whose ages ranged from 2 to 12 years with bipolar disorders, and 20
healthy kids as a control group. The study axes were divided into three parts.
The first part involved determining the levels of gene expression for the Bmal1
and Clock genes using qRT-PCR. The second part is the determination of the levels
of miRNA and snoRNA molecules that regulate Bmal1 and Clock genes using qRT-PCR.
Third part: measuring methylation levels in the promoters of Bmal1 and clock
genes using PCR. The results showed a significant decrease in the Bmal1 gene
expression; it was the value of folding expression Bmal1 gene = 0.73, and a
significant increase in the Clock gene; it was the value of folding expression
Clock gene = 1.23. and the results showed a significant increase in miRNA gene
expression; the value of folding expression for miRNA155/Bmal1 = 1.76, and a
significant decrease in miRNA gene expression; the value of folding expression
for miRNA211/Clock = 0.26. while the gene expression level for snoRNA molecule
= 1.76 compared with control = 1. Conclusion: The results of this study
demonstrate increases in the gene expression folding of the Clock gene and a
significant decrease in miRNA211 gene expression which regulates the Clock gene.
References:
[1].
Parlak, G. C.,
Baris, I., Gul, S., & Kavakli, I. H., 2023, Functional characterization of
the CRY2 circadian clock component variant p. Ser420Phe revealed a new degradation
pathway for CRY2: Journal of Biological Chemistry, 299(12).
[2].
Chen, S. T., Choo,
K. B., Hou, M. F., Yeh, K. T., Kuo, S. J., & Chang, J. G., 2005,
Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers: Carcinogenesis, 26(7),
1241-1246.
[3].
Gršković, P.,
& Korać, P., 2023, Circadian gene variants in diseases: Genes, 14(9),
1703.
[4].
Ramadan, Z. J.,
Hamed, O. M., & Khalaf, I. H., 2020, Detection of genetic variation for
some genes that related with recurrent spontaneous abortion in Nineveh
province: Biochemical & Cellular Archives, 20(2).
[5].
Barragán, R., Sorlí,
J. V., Coltell, O., Gonzalez-Monje, I., Fernández-Carrión, R., Villamil, L. V.,
... & Asensio, E. M., 2022, Influence of
DNA-polymorphisms in selected circadian clock genes on clock gene expression in
subjects from the general population and their association with sleep duration: Medicina, 58(9),
1294.
[6].
Samblas, M., Milagro, F. I., Gómez-Abellán, P.,
Martínez, J. A., & Garaulet, M., 2016, Methylation on the circadian gene
BMAL1 is associated with the effects of a weight loss intervention on serum
lipid levels: Journal of biological rhythms, 31(3), 308-317.
[7].
Alachkar, A., Lee,
J., Asthana, K., Vakil Monfared, R., Chen, J., Alhassen, S., ... & Baldi,
P., 2022, The hidden link between circadian entropy and mental health
disorders: Translational psychiatry, 12(1), 281.
[8].
Merrill, R. M.,
2022, Mental health conditions according to stress and sleep disorders: International
journal of environmental research and public health, 19(13), 7957.
[9].
Liu, C., Tang, X.,
Gong, Z., Zeng, W., Hou, Q., & Lu, R., 2022, Circadian rhythm sleep
disorders: genetics, mechanisms, and adverse effects on health: Frontiers
in Genetics, 13, 875342.
[10]. Hameed, M. A., Hamed, O. M., 2023,
Detection of P53 suppressor gene mutation in women with breast cancer in Mosul
city: AIP Conference ProceedingsThis link is disabled. 2834(1), 020007.
[11]. Hamed, O. M., Al-Taii, R. A., Jankeer,
M. H., 2021, Biochemical and genetic study in blood of β- thalassaemia children
in mosul city, Iraq: Iraqi Journal of ScienceThis link is disabled.
62(8), pp. 2501–2508.
[12]. Al-Hassani, O. M. H., 2020, Role of
MTHFR C667T and MTRR A66G genes polymorphism with thyroid disorders.
In Journal of Physics: Conference Series (Vol. 1660, No. 1, p.
012007). IOP Publishing.
[13]. BaHammam, A. S., & Pirzada, A., 2023, Timing
matters: the interplay between early mealtime, circadian rhythms, gene
expression, circadian hormones, and metabolism—a narrative review: Clocks
& Sleep, 5(3), 507-535.
[14]. Baris, I., Ozcan, O., & Kavakli, I. H., 2023,
Single nucleotide polymorphisms (SNPs) in circadian genes: Impact on gene
function and phenotype: Advances in protein chemistry and structural
biology, 137, 17-37.
[15]. Du, N. H., Arpat, A. B., De Matos, M., Gatfield, D.,
2014, MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide
scale., 3, e02510.
[16]. Mosig, R. A., & Kojima, S., 2022, Timing without
coding: How do long non-coding RNAs regulate circadian rhythms?: In Seminars
in cell & developmental biology Academic Press. (Vol. 126, pp.
79-86).
[17]. Pavithra, S., Aich, A., Chanda, A., Zohra, I. F.,
Gawade, P., & Das, R. K., 2024, PER2 gene and its association with
sleep-related disorders: A review: Physiology & Behavior, 273,
114411.
[18]. Dück, A., Reis, O., Wagner, H., Wunsch, K., Häßler,
F., Kölch, M., ... & Oster, H., 2022, Clock genes profiles as diagnostic
tool in (childhood) ADHD—A pilot study: Brain Sciences, 12(9),
1198.
[19]. Hamed, Owayes. M., 2022, Analysis of Common Mutation
of P53 Gene in Male with Lung Cancer in Mosul City: Bionatura, 7(3),
52.
[20]. Na,Y. J., Sung, J. H., Lee, S. C., Lee, Y. J., Choi,
Y. J., Park, W. Y., Shin, H.S., Kim, J.H., 2009, Comprehensive analysis of
microRNA-mRNA co-expression in circadian rhythm: Exp. Mol. Med. 41,
638–647.
[21]. Faltraco, F., Palm, D., Uzoni, A., Borchert, L.,
Simon, F., Tucha, O., & Thome, J., 2021, Dopamine adjusts the circadian
gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD
patients: Journal of Neural Transmission, 128, 1135-1145.
[22]. Kinoshita, C., Okamoto, Y., Aoyama, K., & Nakaki,
T., 2020, MicroRNA: a key player for the interplay of circadian rhythm
abnormalities, sleep disorders and neurodegenerative diseases: Clocks
& sleep, 2(3), 282-307.
[23]. Haimes, J., Kelley, M., & Dharmacon, Now Part of GE Healthcare, Lafayette, CO, USA., 2013, Demonstration of a ΔΔCq Calculation Method to Compute Thermo Scientific Relative Gene Expression from qPCR Data. Lafayette, CO: Thermo Scientific.
