The Role of miRNA Molecules and DNA-Methylation on Expression of Circadian Rhythm Genes in Kids with Mental Disorders

Download Article

DOI: 10.21522./TAJMHR.2016.05.01.Art010

Authors : Owayes M. Hamed, Zahra J. Ramadan, Elham kh. Abdullah

Abstract:

The variation of circadian rhythm genes is involved in mental disorders in kids, and the disrubance of circadian rhythm considered as a risk factor to the development of most mental disorders. Our aim was to study the estimated the role of miRNA molecules( miRNA24, miRNA449a, and miRNA102 on regulated for Per1, Per2, and Per3) and DNA methylation on gene expression of circadian clock genes .The study sample comprised of 40 patient of kids their ages range between (2 – 12 years ) having mental disorders , and 20 sample of healthy kids  as a control . The study topics were divided into 3 sections: first, determining the level of gene expression for Per1, Per2, and Per3 genes using the qRT-PCR technique. Second section: determination of the level of Non-coding RNA molecules that regulate Per family genes using the qRT-PCR technique. The third section measures the percentage of methylation in the promoter of Per family genes using the PCR technique. The results of the first section showed a significant decrease in the Per1 gene expression; it was the value of folding expression cDNA Per1 gene = 0.33, and a significant increase in the Per2 and Per3 genes; it was the value of folding expression cDNA Per2 gene = 1.76 and folding expression cDNA Per3 gene = 1.58. The results of the second section showed a significant decrease in miRNA gene expression; the value of folding expression cDNA miRNA24 Per1 gene = 0.41, foldin expression cDNA miRNA449a Per2 gene = 0.20, and folding expression cDNA miRNA102 Per3 gene = 0.56. The results of the third section of the DNA methylation showed that DNA methylation in promoter of the Per1 gene was present in 50% of the samples, in the promoter of the Per2 gene, in 43% of the samples, and in the promoter of the Per3 gene, in 0% of the samples.

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 CRY, Journal of Biological Chemistry, JBC299(12).

[2].   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, Medicina58(9), 1294.

[3].   Gršković, P., Korać, P., 2022, Circadian gene variants in diseases, Genes., 14(9), 1703, 2023.

[4].   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.

[5].   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, 137-37.

[6].   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.

[7].   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.

[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].   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.

[10].  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.

[11].  Du, N. H., Arpat, A. B., De Matos, M., Gatfield, D.,2014, MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale, eLife, 3: e02510.

[12].  Na, Y. J., Sung, J. H., Lee, S. C., Lee, Y. J., Choi, Y. J., Park, W. H., Shin, H. S., Kim, J.H., 2005, Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm, Exp. Mol. Med., 41:638–647.

[13].  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.

[14].  Mosig, R. A., Kojima, S.,2022, Timing without coding: How do long non-coding RNAs regulate circadian rhythms?, In Seminars in cell & developmental biology,126, 79-86.

[15].   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.

[16].  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.

[17].  Haimes, J., Kelley, M., 2013, Demonstration of a ΔΔCq Calculation Method to Compute Thermo Scientific Relative Gene Expression from qPCR Data, Lafayette., CO: Thermo Scientific.

[18].  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).

[19].  Hameed, M. A., Hamed, O. M., 2023, Detection of P53 suppressor gene mutation in women with breast cancer in Mosul city, AIP Conference Proceedings, 2834(1), 020007.

[20].  Samblas, M., Milagro, F. I., Gómez-Abellán, P. J. A., Martínez, & 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.

[21].  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 Science, 62(8), pp:2501–2508.

[22].  Salman, R. H., Mortatha, M. B., Nuiaa, R. R., 2024, Data Mining Technique for Diagnosing Autism Spectrum Disorder, Iraqi Journal of Science, 5239-5253.