Extracellular vesicle-mediated delivery of anti-miR-106b inhibits morphine-induced primary ciliogenesis in the brain

Ma, Rong; Kutchy, Naseer A.; Wang, Zhongbin; Hu, Guoku

doi:10.1016/j.ymthe.2023.03.030

Cited by 6 publications

(1 citation statement)

References 103 publications

(126 reference statements)

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“…[ 51 ] Reportedly, in morphine‐treated astrocytes, EVs containing miR‐106b can promote ciliogenesis in cells by downregulating CEP97. [ 52 ] Furthermore, in human β‐cells, colocalization of G3BP1‐RFP and CD63‐GFP (EV marker) indicates that stress granules and EVs are present together, and the contents of stress granules can be incorporated into EVs. [ 53 ] Therefore, G3BPs and HDAC6, two key components of stress granules, can be readily recruited by EVs.…”

Section: Discussionmentioning

confidence: 99%

The miR‐669a‐5p/G3BP/HDAC6/AKAP12 Axis Regulates Primary Cilia Length

Wang,

Dai,

et al. 2023

Advanced Science

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Primary cilia are conserved organelles in most mammalian cells, acting as “antennae” to sense external signals. Maintaining a physiological cilium length is required for cilium function. MicroRNAs (miRNAs) are potent gene expression regulators, and aberrant miRNA expression is closely associated with ciliopathies. However, how miRNAs modulate cilium length remains elusive. Here, using the calcium‐shock method and small RNA sequencing, a miRNA is identified, namely, miR‐669a‐5p, that is highly expressed in the cilia‐enriched noncellular fraction. It is shown that miR‐669a‐5p promotes cilium elongation but not cilium formation in cultured cells. Mechanistically, it is demonstrated that miR‐669a‐5p represses ras‐GTPase‐activating protein SH3‐domain‐binding protein (G3BP) expression to inhibit histone deacetylase 6 (HDAC6) expression, which further upregulates A‐kinase anchor protein 12 (AKAP12) expression. This effect ultimately blocks cilia disassembly and leads to greater cilium length, which can be restored to wild‐type lengths by either upregulating HDAC6 or downregulating AKAP12. Collectively, these results elucidate a previously unidentified miR‐669a‐5p/G3BP/HDAC6/AKAP12 signaling pathway that regulates cilium length, providing potential pharmaceutical targets for treating ciliopathies.

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Section: Discussionmentioning

confidence: 99%