MicroRNA-7: expression and function in brain physiological and pathological processes

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level and play critical roles in regulating physiological function, and are becoming worldwide research hot spot in brain development and diseases. However, the exact value of miRNAs in brain physiological and pathological processes remain to be fully elucidated, which is vital for the application of miRNAs as diagnostic, prognostic, and therapeutic biomarkers for brain diseases. MicroRNA-7 (miR-7), as a highly expressed miRNA molecule in the mammalian brain, is well documented to play a critical role in development of various diseases. Importantly, accumulating evidence has shown that miR-7 is involved in a range of developmental and pathological processes of brain. Expressively, miR-7, encoded by three genes located different chromosomes, is dominantly expressed in neurons with sensory or neurosecretory. Moreover, the expression of miR-7 is regulated at three levels including gene transcription, process of primary and precursor sequence and formation of mature sequence. Physiologically, miR-7 principally governs the physiological development of Pituitary gland, Optic nervous system and Cerebral cortex. Pathologically, miR-7 can regulate multiple genes thereby manipulating the process of various brain diseases including neurodegenerative diseases, neuroinflammation, and mental disorders and so on. These emerging studies have shown that miR-7, a representative member of miRNA family, might be a novel intrinsic regulatory molecule involved in the physiological and pathological process of brain. Therefore, in-depth studies on the role of miR-7 in brain physiology and pathology undoubtedly not only provide a light on the roles of miRNAs in brain development and diseases, but also are much helpful for ultimate development of therapeutic strategies against brain diseases. In this review, we provide an overview of current scientific knowledge regarding the expression and function of miR-7 in development and disease of brain and raise many issues involved in the relationship between miR-7 and brain physiological and pathological processes.

Whole-genome sequencing reveals new Alzheimer’s disease-associated rare variants in loci related to synaptic function and neuronal development

“…A resource for experimental characterization of lincRNA (lncBase v2 database), reveals that LINC00298 contains an experimentally supported microRNA binding site for miR- 7, discovered by brain high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) experiments 23 . miR-7 is expressed highly in the brain and has been implicated in numerous mechanisms in neurodevelopment, healthy brain function as well as in brain diseases, including AD, neuroinflammation, Lewy body dementia, psychiatric disorders, and Parkinson’s disease 24 . Of the 73 rare-variant-associated genes co-expressed with LINC00298 in our study, 17 are included in protein- protein interactions with our newly AD-associated genes, including APC (corr 0.449) and CTNNA2 (corr 0.381) (Fig.…”

The Role of miRNA-7 in the Biology of Cancer and Modulation of Drug Resistance

“…Pri-miR-7-1 and pri-miR-7-3 lie within introns of the heterogeneous nuclear ribonucleoprotein K-encoding gene ( HNRNPK ) and pituitary specific factor 1 gene ( PIT1 ), respectively. The pri-miR-7-2-encoding gene is placed in the intergenic region of chromosome 15 [ 38 , 39 ]. Originally, miR-7 referred to miR-7-5p, since it seemed to be the only mature miRNA from all three precursors that affects cellular pathways.…”

“…MiR-7 is particularly critical in tissue of neuroendocrine origin, such as pancreas or brain. It plays an important role in the development and differentiation of those organs [ 39 ]. The hypothalamus and pituitary gland are especially enriched in miR-7, in contrast to the cerebellum, cerebral cortex, striatum, or substantia nigra, where its expression is lower.…”

“…Such an arrangement may be the result of the presence of MIR7-3 in the intron of the PIT1 -encoding gene. In the pituitary gland, miR-7 is involved in regulating the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) via the prostaglandin F2 receptor negative regulator (PTGRF) [ 39 ]. Moreover, miR-7 represses the translation of paired box gene 6 ( PAX6 ; important factor in brain and eye organogenesis) by targeting two sites in the 3′UTR [ 88 ].…”

Dysregulation of microRNA and Intracerebral Hemorrhage: Roles in Neuroinflammation

“…In normal physiology, miR-7 regulates the development of the pituitary gland, optic nerve system, and cerebral cortex [ 74 ]. In contrast, dysregulated miR-7 expression is associated with a variety of pathological conditions, such as cellular metastasis [ 75 ], α-synuclein accumulation [ 76 ], amyloid peptide accumulation [ 77 ], and apoptosis [ 78 ].…”