LncRNA Pnky Positively Regulates Neural Stem Cell Migration by Modulating mRNA Splicing and Export of Target Genes

Du, Jiannan; Li, Yuan; Su, Yu-Ting; Zhi, Wenqian; Zhang, Jiale; Zhang, Cheng; Wang, Juan; Deng, Wensheng; Zhao, Shasha

doi:10.1007/s10571-022-01241-4

Cited by 10 publications

(5 citation statements)

References 77 publications

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“…To induce PLEKHA4 silencing, siRNAs were transfected into LN229 cells for 48 h using Lipofectamine RNAiMAX (Thermo Fisher, Scientific, USA). The knockdown efficiency was then verified using RT-qPCR method as described previously ( 39 ). To polarize M0 to M1 macrophages, 2.5×10 5 THP-1 cells were seeded into 6-well plate and stimulated with 320 nM phorbol-12-myristate-13-acetate (PMA; Beyotime Biotechnology, China) at 37°C for 6 h. To polarize M2 macrophages, cells were further incubated with IL-4 (20 ng/ml; Beyotime) and IL-13 (20 ng/ml; Beyotime) for 72 h at 37°C ( 24 , 40 ).…”

Section: Methodsmentioning

confidence: 99%

“…To polarize M0 to M1 macrophages, 2.5×10 5 THP-1 cells were seeded into 6-well plate and stimulated with 320 nM phorbol-12-myristate-13-acetate (PMA; Beyotime Biotechnology, China) at 37°C for 6 h. To polarize M2 macrophages, cells were further incubated with IL-4 (20 ng/ml; Beyotime) and IL-13 (20 ng/ml; Beyotime) for 72 h at 37°C ( 24 , 40 ). Identification of THP-1 derived M2 macrophages was performed using immunofluorescence (IF) staining for CD163 (ab182422, Abcam; 1:1500 dilution), as reported earlier ( 39 ).…”

Section: Methodsmentioning

confidence: 99%

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PLEKHA4 is a novel prognostic biomarker that reshapes the tumor microenvironment in lower-grade glioma

Zhi,

Wang,

Jiang

et al. 2023

Front. Immunol.

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BackgroundLower-grade glioma (LGG) is a primary intracranial tumor that carry a high risk of malignant transformation and limited therapeutic options. Emerging evidence indicates that the tumor microenvironment (TME) is a superior predictor for tumor progression and therapy response. PLEKHA4 has been demonstrated to be a biomarker for LGG that correlate with immune infiltration. However, the fundamental mechanism by which PLEKHA4 contributes to LGG is still poorly understood.MethodsMultiple bioinformatic tools, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA2), Shiny Methylation Analysis Resource Tool (SMART), etc., were incorporated to analyze the PLEKHA4. ESTIMATE, ssGSEA, CIBERSORT, TIDE and CellMiner algorithms were employed to determine the association of PLEKHA4 with TME, immunotherapy response and drug sensitivities. Immunohistochemistry (IHC)-based tissue microarrays and M2 macrophage infiltration assay were conducted to verify their associations.ResultsPLEKHA4 expression was found to be dramatically upregulated and strongly associated with unfavorable overall survival (OS) and disease-specific survival (DSS) in LGG patients, as well as their poor clinicopathological characteristics. Cox regression analysis identified that PLEKHA4 was an independent prognostic factor. Methylation analysis revealed that DNA methylation correlates with PLEKHA4 expression and indicates a better outcome in LGG. Moreover, PLEKHA4 was remarkably correlated with immune responses and TME remodeling, as evidenced by its positive correlation with particular immune marker subsets and the putative infiltration of immune cells. Surprisingly, the proportion of M2 macrophages in TME was strikingly higher than others, inferring that PLEKHA4 may regulate the infiltration and polarization of M2 macrophages. Evidence provided by IHC-based tissue microarrays and M2 macrophage infiltration assay further validated our findings. Moreover, PLEKHA4 expression was found to be significantly correlated with chemokines, interleukins, and their receptors, further supporting the critical role of PLEKHA4 in reshaping the TME. Additionally, we found that PLEKHA4 expression was closely associated with drug sensitivities and immunotherapy responses, indicating that PLEKHA4 expression also had potential clinical significance in guiding immunotherapy and chemotherapy in LGG.ConclusionPLEKHA4 plays a pivotal role in reshaping the TME of LGG patients, and may serve as a potential predictor for LGG prognosis and therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

PLEKHA4 is a novel prognostic biomarker that reshapes the tumor microenvironment in lower-grade glioma

Zhi,

Wang,

Jiang

et al. 2023

Front. Immunol.

Self Cite

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“…lncRNA Pnky overexpression has enhanced the protein levels of some critical regulators of neural stem cell migration, including Cx43, whereas lncRNA Pnky depletion has decreased them in vitro. Consistently, cells overexpressing lncRNA Pnky transplanted into mice exhibited greater migration distances in the spinal canal than those in which lncRNA Pnky was depleted [ 31 ]. Knockdown of lncRNA NEAT1 downregulated Cx32 expression via the promotion of miR-1301-3p, a suppressor of Gjb1 (Cx32); suppressed the α-synuclein-induced inflammatory response; and reduced apoptosis in a cellular Parkinson’s disease (PD) model [ 32 ].…”

Section: Disorders Modulated By Noncoding Rnas Through Relevant Conne...mentioning

confidence: 96%

“…lncRNAs also function as the regulators of several CNS diseases [ 29 , 30 ]. lncRNA Pnky has a modulatory effect on Cx43 during neural stem cell migration [ 31 ]. lncRNA Pnky overexpression has enhanced the protein levels of some critical regulators of neural stem cell migration, including Cx43, whereas lncRNA Pnky depletion has decreased them in vitro.…”

Section: Disorders Modulated By Noncoding Rnas Through Relevant Conne...mentioning

confidence: 99%

Perspective and Therapeutic Potential of the Noncoding RNA–Connexin Axis

Li,

Wang,

Chen

2024

IJMS

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Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary sequences of mRNAs or other ncRNAs or by directly engaging in protein interactions. Over the past few decades, the pervasiveness of ncRNAs in cell physiology and their pivotal roles in various diseases have been identified. One target regulated by ncRNAs is connexin (Cx), a protein that forms gap junctions and hemichannels and facilitates intercellular molecule exchange. The aberrant expression and misdistribution of connexins have been implicated in central nervous system diseases, cardiovascular diseases, bone diseases, and cancer. Current databases and technologies have enabled researchers to identify the direct or indirect relationships between ncRNAs and connexins, thereby elucidating their correlation with diseases. In this review, we selected the literature published in the past five years concerning disorders regulated by ncRNAs via corresponding connexins. Among it, microRNAs that regulate the expression of Cx43 play a crucial role in disease development and are predominantly reviewed. The distinctive perspective of the ncRNA–Cx axis interprets pathology in an epigenetic manner and is expected to motivate research for the development of biomarkers and therapeutics.

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“…Pnky is an evolutionarily conserved, neural lncRNA that regulates mouse neural stem cell (NSC) function both in vitro and in vivo (Ramos et al 2015; Andersen et al 2019). Pnky conditional knockout (cKO) (Andersen et al 2019) or transcript knockdown (KD) (Ramos et al 2015; Lin et al 2014) increases neuronal production from cultured mouse NSCs, and other studies indicate a role for Pnky in NSC migration (Du et al 2023). In vivo , genetic deletion of Pnky – either cKO or germline KO – causes aberrant cortical development, resulting in alterations of neuron subtype abundance (Andersen et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Sex-specific role for the long noncoding RNAPnkyin mouse behavior

Saha,

Andersen,

Hong

et al. 2023

Preprint

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SUMMARYThe human brain expresses thousands of different long noncoding RNAs (lncRNAs), and aberrant expression of specific lncRNAs has been associated with cognitive and psychiatric disorders. While a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few have been shown to underlie animal behavior, particularly with genetic strategies that establish lncRNA function intrans.Pnkyis an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show thatPnkyhas sex-specific roles in mouse behavior and that this lncRNA underlies specific behavior by functioning intrans. MalePnky-knockout (KO) mice have deficits in cued fear recall, a type of Pavlovian associative memory. In femalePnky-KO mice, the acoustic startle response (ASR) is increased and accompanied by a decrease in prepulse inhibition (PPI), both of which are behaviors altered in affective disorders. Remarkably, expression ofPnkyfrom a bacterial artificial chromosome (BAC) transgene reverses the ASR phenotype of femalePnky-KO mice, demonstrating thatPnkyunderlies specific animal behavior by functioning intrans. More broadly, these data provide genetic evidence that a lncRNA gene and its function intranscan play a key role in the behavior of adult mammals, contributing fundamental knowledge to our growing understanding of the association between specific lncRNAs and disorders of cognition and mood.

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LncRNA Pnky Positively Regulates Neural Stem Cell Migration by Modulating mRNA Splicing and Export of Target Genes

Cited by 10 publications

References 77 publications

PLEKHA4 is a novel prognostic biomarker that reshapes the tumor microenvironment in lower-grade glioma

PLEKHA4 is a novel prognostic biomarker that reshapes the tumor microenvironment in lower-grade glioma

Perspective and Therapeutic Potential of the Noncoding RNA–Connexin Axis

Sex-specific role for the long noncoding RNAPnkyin mouse behavior

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