Contribution

This year, our team’s contribution is based on the 2022 ICJFLS team who created four different parts to diagnose major depressive disorder (MDD). The 2022 ICJFLS team reported that three micro RNAs (miRNAs) were upregulated in the serum and cerebrospinal fluid (CSF) of MDD patients [1]. According to the 2022 ICJFLS team, miRNA 34a-5p, miRNA 221-3p, and miRNA let-7d-3p are upregulated in MDD patients. Thus, these miRNAs can be used as potential biomarkers for MDD. Subsequently, the 2022 ICJFLS team designed four toehold switch parts, each carrying a different reporter gene, to detect miRNA and thus diagnose MDD. The parts and their functions are shown in Table 1.

Table 1. Parts and their functions.

Part name	miRNA	Reporter gene	Color
BBa_K4167000	miRNA 34a-5p	Amil CP	Black
BBa_K4167001	miRNA 221-3p	mRFP1	Red
BBa_K4167002	miRNA let-7d-3p	amilGFP	Yellow
BBa_K4167666	miRNA 34a-5p	lacZ	Blue

Here we provide further information to support their project and extend beyond their findings.

According to Al-Rawaf et al. [2] and Kuang et al. [3], miRNA 34a-5p was upregulated in the serum of MDD patients, as shown in Figure 1A. According to Feng et al. [4] and Kuang et al. [3], miRNA 221-3p was upregulated in the serum of MDD patients, as shown in Figure 1B. Meanwhile, Bahi et al. [5] and Mendes-Silva et al. [6] reported increased miRNA let-7d-3p concentrations in MDD patient serum as shown in Figure 1C. The above findings all support the 2022 ICJFLS team and their project.

Figure 1. (A) microRNAs' differential expression profile in healthy control and older adults with depression. (B) miR-34a-5p' expression in the depressed patients before and 8 weeks after antidepressant treatment. (C) Anxiety- and Depression-like behaviors like behavior in Mock- and let-7d-injected mice in the tail suspension test.

However, we also noticed that miRNA 34a-5p was downregulated in some other MDD patient tissues, including the anterior cingulate cortex (AnCg) [7] and the Brodmann area [8] This implies major differences in cellular activity and metabolism among cells of different tissues in MDD patients, leaving room for future research.

Furthermore, many other researchers have reported findings of other miRNAs in MDD patient tissues, including miR-363-5p [9], miRNA 218-5p [10], and miRNA 320a-5p [10], as shown in Figure 2. Therefore, new parts can be designed to target the above biomarkers and support MDD diagnosis.

Figure 2. The serum expression analysis of miR-218-5p and miR-320a-5p between depressed PD patients and healthy controls through RT-qPCR.

In addition to miRNAs, several types of long non-coding RNA (lncRNA) are also expressed at abnormal levels in MDD patient tissue and can serve as biomarkers for the disease. Examples include TCONS_l2_00001212, NONHSAT102891, and TCONS_00019174 were downregulated, while ENST00000517573 was upregulated [13].

Additionally, many other types of molecules also exist at abnormal levels in MDD patient tissues, making them potential biomarkers for MDD. Examples include Immunoglobulin A, estrogen, serotonin, Plasma C-reactive protein, g-aminobutyric acid, and cortisol [12, 13].

This year, our YiYe-China team is utilizing the secondary structure of mRNA to diagnose gastric cancer. Through our process, we used the RNAfold website to predict mRNA secondary structures. Many research topics involve RNA secondary structures, but currently, programs such as RNAfold are not used very frequently as it is relatively new. Here, we suggest that such computer programs will provide substantial help to RNA-related research in the future.

References

[1] ICJFLS team. “Project Description.” IGEM, 2022.igem.wiki/icjfls/description.

[2] Al-Rawaf, Hadeel A., et al. “Circulating MicroRNAs and Molecular Oxidative Stress in Older Adults with Neuroprogression Disorders.” Disease Markers, vol. 2021, 22 Oct. 2021, pp. 1–10, https://doi.org/10.1155/2021/4409212

[3] Kuang, Wei-Hong, et al. “MicroRNA-451a, MicroRNA-34a-5p, and MicroRNA-221-3p as Predictors of Response to Antidepressant Treatment.” Brazilian Journal of Medical and Biological Research, vol. 51, no. 7, 2018, https://doi.org/10.1590/1414-431x20187212

[4] Feng, Jianguo, et al. “Serum MiR-221-3p as a New Potential Biomarker for Depressed Mood in Perioperative Patients.” Brain Research, vol. 1720, Oct. 2019, p. 146296, https://doi.org/10.1016/j.brainres.2019.06.015

[5] Amine Bahi, and Jean-Luc Dreyer. “Lentiviral-Mediated Let-7d MicroRNA Overexpression Induced Anxiolytic- and Anti-Depressant-like Behaviors and Impaired Dopamine D3 Receptor Expression.” European Neuropsychopharmacology, vol. 28, no. 12, 20 Sept. 2018, pp. 1394–1404, https://doi.org/10.1016/j.euroneuro.2018.09.004

[6] Mendes-Silva, Ana Paula, et al. “Shared Biologic Pathways between Alzheimer Disease and Major Depression: A Systematic Review of MicroRNA Expression Studies.” The American Journal of Geriatric Psychiatry, vol. 24, no. 10, Oct. 2016, pp. 903–912, https://doi.org/10.1016/j.jagp.2016.07.017

[7] Azevedo, Joshua A., et al. “The MicroRNA Network Is Altered in Anterior Cingulate Cortex of Patients with Unipolar and Bipolar Depression.” Journal of Psychiatric Research, vol. 82, 1 Nov. 2016, pp. 58–67, www.sciencedirect.com/science/article/pii/S0022395616301431, https://doi.org/10.1016/j.jpsychires.2016.07.012

[8] Smalheiser, Neil R., et al. “MicroRNA Expression Is Down-Regulated and Reorganized in Prefrontal Cortex of Depressed Suicide Subjects.” PLoS ONE, vol. 7, no. 3, 9 Mar. 2012, p. e33201, https://doi.org/10.1371/journal.pone.0033201

[9] Liu L, Wang H, Yu Y, et al. Microbial regulation of a lincRNA-miRNA-mRNA network in the mouse hippocampus. Epigenomics. 2020;12(16):1377-1387. doi:10.2217/epi-2019-0307

[10] Wan, Zhirong, et al. “MiR-218-5p and MiR-320a-5p as Biomarkers for Brain Disorders: Focus on the Major Depressive Disorder and Parkinson’s Disease.” Molecular Neurobiology, vol. 60, no. 10, 17 June 2023, pp. 5642–5654, https://doi.org/10.1007/s12035-023-03391-y

[11] Cui, Xuelian, et al. “Long Non-Coding RNA: Potential Diagnostic and Therapeutic Biomarker for Major Depressive Disorder.” Medical Science Monitor, vol. 22, 31 Dec. 2016, pp. 5240–5248, https://doi.org/10.12659/msm.899372.

[12] Kennis, Mitzy, et al. "Prospective Biomarkers of Major Depressive Disorder: A Systematic Review and Meta-Analysis." Molecular Psychiatry, vol. 25, 2020, pp. 321–338. https://doi.org/10.1038/s41380-019-0585-z

[13] Zhang, Xin, et al. “Early-Diagnosis of Major Depressive Disorder: From Biomarkers to Point-of-Care Testing.” TrAC Trends in Analytical Chemistry, vol. 159, Feb. 2023, p. 116904, https://doi.org/10.1016/j.trac.2022.116904.