LncRNA of Peripheral Blood Mononuclear Cells: HYMAI Acts as a Potential Diagnostic and Therapeutic Biomarker for Female Major Depressive Disorder Author names and affiliations

Tianyi Bu ¹ Jiarun Yang ^2* Jiawei Zhou ^1* Yeran Liu ^1* Kexin Qiao ^1* Yan Wang ^1* Ji Li Zhang ^1* Boakye Kwame Owura ^1* Yanjie Yang ^1* Zhengxue Qiao ^1* Xiaohui Qiu ^1*

• ¹ Harbin Medical University, Harbin, Heilongjiang, China
• ² Heilongjiang University, Harbin, Heilongjiang Province, China

Introduction: Although major depressive disorder (MDD) has brought huge burden and challenges to society globally, the objective and accurate diagnoses and treatments criteria remain improvement. It is well documented that lncRNAs have taken part in neurodevelopmental, neurodegenerative and psychiatric diseases, however, the investigation of the function of lncRNAs in MDD is still in its relative infancy. It is necessary to take sex differences into account when explore the pathogenesis as well. The study aim to explore potential diagnostic biomarkers of female MDD and then investigated its regulatory role in MDD pathogenesis . Methods: First, the full expression profile of lncRNAs in PBMCs between two groups has been established based on high-throughput sequencing analysis. In addition, 5 deferentially expressed lncRNAs were quantified by quantitative real-time PCR to explore potential biomarker. To further investigate the function of biomarker in the pathogenesis of MDD, bioinformatics analysis on downstream target genes was carried out. Results: The expression profile showed that 300 DElncRNAs has been screened. Among the 5 selected deferentially expressed lncRNAs, HYMAI was proved to be the potential diagnostic biomarker. Its expression levels was significantly higher in patients with MDD than in healthy controls with high potential diagnostic value (AUC=0.867; 95% CI 0.809-0.925, p<0.0001). To explain the competing endogenous RNA role of HYMAI, a HYMAI-miRNA-mRNA network was established. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses stated that some of the enriched pathways downstream of HYMAI are closely related to MDD. Moreover, protein-protein network was established to further screen out the hub genes (SNAI2, GSK-3β, DVL1, FZD5, THBS1, VANGL1, RUNX1, COL4A1, TGFβ2 and REST). Conclusion: It is clarified that the dysregulated expression of HYMAI may be the pathophysiological basis of women suffering from MDD. The findings also contribute to insight into the molecular mechanism of women's susceptibility to MDD.