tiRNA-Gly-GCC-001 in major depressive disorder: Promising diagnostic and therapeutic biomarker

Haihua Tian; Shugui Gao; Miaomiao Xu; Mei Yang; Mengyuan Shen; Jimeng Liu; Guangxue Li; Dingding Zhuang; Zhenyu Hu; Chuang Wang

doi:10.1111/bph.16319

tiRNA-Gly-GCC-001 in major depressive disorder: Promising diagnostic and therapeutic biomarker

Br J Pharmacol. 2024 Mar 4. doi: 10.1111/bph.16319. Online ahead of print.

Authors

Haihua Tian^{1

2

3}, Shugui Gao^{2

3}, Miaomiao Xu^{2

3}, Mei Yang^{2

3}, Mengyuan Shen^{2

3}, Jimeng Liu^{2

3}, Guangxue Li^{2

3}, Dingding Zhuang^{2

3}, Zhenyu Hu^{2

3}, Chuang Wang¹

Affiliations

¹ Zhejiang Key Laboratory of Pathophysiology, Health Center, Ningbo University, Ningbo, Zhejiang, China.
² Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China.
³ Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.

PMID: 38439581
DOI: 10.1111/bph.16319

Abstract

Background and purpose: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development.

Experimental approach: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA-Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed.

Key results: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up-regulated and 4 down-regulated). qRT-PCR was used to validate the expression of six tsRNAs that were up-regulated in MDD (tiRNA-1:20-chrM.Ser-GCT, tiRNA-1:33-Gly-GCC-1, tRF-1:22-chrM.Ser-GCT, tRF-1:31-Ala-AGC-4-M6, tRF-1:31-Pro-TGG-2 and tRF-1:32-chrM.Gln-TTG). Interestingly, serum tiRNA-Gly-GCC-001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA-Gly-GCC-001 is predicted to suppress brain-derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA-Gly-GCC-001 down-regulation was evident following an 8-week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy.

Conclusion and implications: Our current work reports for the first time that tiRNA-Gly-GCC-001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.

Keywords: bioinformatics analysis; brain-derived neurotrophic factor (BDNF); high-throughput sequencing; major depressive disorder (MDD); transfer RNA-derived small ribonucleic acids (tsRNAs).

Abstract

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