☆ 4.6 Review

The emerging role of long non-coding RNAs in schizophrenia

FRONTIERS IN PSYCHIATRY (2022)

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Involvement of the long intergenic non-coding RNA LINC00461 in schizophrenia

Shuquan Rao et al.

Summary: This study identifies the potential role of LINC00461 gene in the development of schizophrenia. The risk variant of LINC00461 gene is significantly associated with the disease and is linked to smaller hippocampal volume. Moreover, the blood expression level of LINC00461 mRNA is significantly lower in schizophrenia patients.

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Article Biochemistry & Molecular Biology

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Summary: This study explores the role of lncRNAs, miRNAs, and circRNAs in the pathobiology of Autism Spectrum Disorders (ASD).

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Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia

Michel Cuenod et al.

Summary: There is a pathological link between oxidative stress and schizophrenia, with oxidative stress playing a central role in the impairment of neural circuits and subsequent cognitive, emotional, social, and sensory deficits characteristic of the disorder. Redox dysregulation, NMDA receptor hypofunction, neuroinflammation, and mitochondria dysfunction exacerbate this damage, creating a vicious cycle that leads to persistent impairments in neural circuit synchronization. Therapeutic approaches targeting these cycles show promise for interventions, and a reverse translation of circuitry approaches is needed for improved early detection and successful clinical trials in precision medicine for psychiatry.

MOLECULAR PSYCHIATRY (2022)

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Article Genetics & Heredity

Genome-wide association studies-supported rs12966547 variant of the long noncoding RNA LOC105372125 is significantly associated with susceptibility to schizophrenia and bipolar disorder in Han Chinese women

Zhi Zhao et al.

Summary: This study analyzed the association between LOC105372125 rs12966547 polymorphism and schizophrenia and bipolar disorder in the Han Chinese population. The results showed a significant association between rs12966547 polymorphism and bipolar disorder in women, as well as an association with schizophrenia in women. However, no significant association was found in men.

PSYCHIATRIC GENETICS (2022)

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Letter Psychiatry

Aberrant expressions of MIAT and PVT1 in serum exosomes of schizophrenia patients

Chuang Guo et al.

SCHIZOPHRENIA RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Upregulation of VDR-associated lncRNAs in Schizophrenia

Soudeh Ghafouri-Fard et al.

Summary: The study found that Vitamin D receptor (VDR) signaling is associated with long non-coding RNAs (lncRNAs) in the pathology of schizophrenia. In patients with schizophrenia, the expression levels of SNHG6, LINC00346, and LINC00511 were significantly increased, suggesting potential as markers for schizophrenia.

JOURNAL OF MOLECULAR NEUROSCIENCE (2022)

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Structural basis for mismatch surveillance by CRISPR-Cas9

Jack P. K. Bravo et al.

Summary: In this study, the structure of Cas9 during mismatch cleavage was determined using kinetics-guided cryo-electron microscopy. It was found that a linear conformation of the guide RNA-DNA duplex formed in the presence of mismatches, preventing Cas9 activation. Additionally, mismatches distal to the protospacer adjacent motif were stabilized by reorganization of a loop in the RuvC domain. Mutations of mismatch-stabilizing residues reduced off-target DNA cleavage while maintaining rapid on-target DNA cleavage. This study provides proof of concept for the design of next-generation high-fidelity Cas9 variants targeting mismatch tolerance regions.

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Article Clinical Neurology

Emerging roles of long non-coding RNA in depression

Wen-Zhi Hao et al.

Summary: Depression is a common psychiatric disorder with unclear underlying mechanisms. Recent research suggests that long non-coding RNAs (lncRNA) play a regulatory role in depression, mediating its development through various pathways. Additionally, lncRNAs may serve as potential biomarkers for differential diagnosis of depression and other mental illnesses. Further exploration is needed to understand the therapeutic targets and diagnostic biomarkers of lncRNAs in depression.

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY (2022)

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Pilong Shi et al.

Summary: Cardiac microvascular dysfunction is associated with cardiac hypertrophy and heart failure. Dysregulation of long non-coding RNAs (lncRNAs) plays a key role in cardiac hypertrophy. This study identified a lncRNA, AAB, that is upregulated in cardiac hypertrophy rats and in Ang II-induced cardiac microvascular endothelial cells (CMECs). LncRNA AAB sponges miR-30b-5p, leading to an imbalance of MMP9/TIMP1 and activation of transferrin receptor 1 (TFR-1), which ultimately leads to ferroptosis of CMECs. Additionally, a delivery system based on neutrophil membrane-camouflaged mesoporous silica nanocomplex (MSN) was developed for the inhibition of cardiac hypertrophy, indicating the potential of targeting lncRNA AAB as a novel therapy for cardiac hypertrophy.

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Immune System Abnormalities in Schizophrenia: An Integrative View and Translational Perspectives

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Summary: The immune system abnormalities are associated with the pathogenesis of schizophrenia, and immune parameters may help identify subgroups with signs of inflammation. Gaps in knowledge about immune abnormalities in schizophrenia have been identified.

FRONTIERS IN PSYCHIATRY (2022)

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Chunhui Li et al.

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Ji He et al.

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Xabier Osteikoetxea et al.

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LncRNA RP5-998N21.4 promotes immune defense through upregulation of IFIT2 and IFIT3 in schizophrenia

Bo Guo et al.

Summary: The long noncoding RNA RP5-998N21.4 plays a critical role in regulating immune defense and may contribute to the onset of schizophrenia. It positively regulates the transcription of IFIT2 and IFIT3 and enhances immune defense responses. These findings have important implications for understanding the etiology and potential therapeutic strategies for schizophrenia.

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LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia

Chaoying Ni et al.

Summary: The study identified a schizophrenia-associated upregulated long noncoding RNA in monozygotic twins, revealing its involvement in the disease by affecting the inflammatory response. By regulating the DNA methylation of the transcriptional repressor CIC, it influences the expression of SOCS3 and CASP1, improving the inflammatory response.

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Yuanyuan Chen et al.

Summary: Extensive studies have shown that long non-coding RNAs (lncRNAs) play crucial roles in physiological processes and are closely linked to various diseases. Using lncRNAs as biomarkers or intervention targets can provide new perspectives for disease diagnosis and treatment. Research is shifting towards utilizing lncRNAs as pharmacological targets, with a focus on preclinical research and clinical trial progress.

ACTA PHARMACEUTICA SINICA B (2021)

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Association study of a genetic variant in the long intergenic noncoding RNA (linc01080) with schizophrenia in Han Chinese

Yi Qi et al.

Summary: This study examined the association between the single nucleotide polymorphism (SNP) rs7990916 in linc01080 and susceptibility to schizophrenia in a Southern Chinese Han population. The results showed that the SNP was significantly associated with age of onset and cognitive function in schizophrenia patients, indicating a potential role of linc01080 polymorphism in the pathogenesis of schizophrenia.

BMC PSYCHIATRY (2021)

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LNCcation: lncRNA localization and function

Mary Catherine Bridges et al.

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Expression of BDNF-Associated lncRNAs in Treatment-Resistant Schizophrenia Patients

Elham Badrlou et al.

Summary: Long non-coding RNAs (lncRNAs) play a crucial role in the central nervous system development and neuronal modulation. Abnormal expression patterns of transcripts like BDNF and associated lncRNAs were found in schizophrenia patients. PNKY showed the highest diagnostic power in identifying disease status, suggesting its potential as a diagnostic marker for schizophrenia.

JOURNAL OF MOLECULAR NEUROSCIENCE (2021)

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Review Cell Biology

Gene regulation by long non-coding RNAs and its biological functions

Luisa Statello et al.

Summary: Recent studies have shed new light on the biogenesis and functions of long non-coding RNAs (lncRNAs), showcasing their diverse roles in gene regulation and signaling pathways, particularly in the contexts of neuronal disorders, immune responses, and cancer. The discovery of unique biogenesis pathways and subcellular localizations of lncRNAs has opened up potential therapeutic avenues for targeting lncRNAs in various biological and pathophysiological conditions.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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siRNA Specificity: RNAi Mechanisms and Strategies to Reduce Off-Target Effects

Julia Neumeier et al.

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CRISPR-CasRx Targeting LncRNA LINC00341 Inhibits Tumor Cell Growth in vitro and in vivo

Chunjing Li et al.

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Machine Learning Reduced Gene/Non-Coding RNA Features That Classify Schizophrenia Patients Accurately and Highlight Insightful Gene Clusters

Yichuan Liu et al.

Summary: Machine learning has been used to reduce functional biomarkers in schizophrenia patients, with long non-coding RNAs (lncRNAs) capturing the characteristics of SCZ tissue more accurately than mRNA.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

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