Ion channel long non-coding RNAs in neuropathic pain

Felix, Ricardo; Muñoz-Herrera, David; Corzo-López, Alejandra; Fernández-Gallardo, Miriam; Leyva-Leyva, Margarita; González‐Ramírez, Ricardo; Sandoval, Alejandro

doi:10.1007/s00424-022-02675-x

Cited by 6 publications

(5 citation statements)

References 127 publications

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“…Our results suggest that the expression of CACNG2-DT increases the Ca V γ 2 /Stg protein levels, reinforcing the idea that the promoter of the CACNG2 gene is bidirectional and that one of its gene products is a lncRNA. This finding further provides experimental evidence for the regulated co-expression of the lncRNA-protein pair reported for other similarly organized genes ( Guttman and Rinn, 2012 ; Hombach and Kretz, 2016 ; Bridges et al, 2021 ; Felix et al, 2022 ).…”

Section: Discussionsupporting

confidence: 76%

“…Finally, it is also known that lncRNAs are >200 bp RNA molecules that are not translated ( Guttman and Rinn, 2012 ; Hombach and Kretz, 2016 ; Bridges et al, 2021 ; Felix et al, 2022 ) and may have different regulatory functions in the transcription of various genes and the translation of several proteins, including ion channel subunits ( Felix et al, 2022 ). Interestingly, here we show that CACNG2-DT may increase the expression of Ca V γ 2 /Stg, providing relevant information into the molecular mechanisms that regulate the expression of this intriguing synaptic protein.…”

Section: Introductionmentioning

confidence: 99%

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Molecular cloning of the gene promoter encoding the human CaVγ2/Stargazin divergent transcript (CACNG2-DT): characterization and regulation by the cAMP-PKA/CREB signaling pathway

Muñoz-Herrera,

Calderón-Rivera,

Zarco

et al. 2023

Front. Physiol.

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CaVγ2 (Stargazin or TARPγ2) is a protein expressed in various types of neurons whose function was initially associated with a decrease in the functional expression of voltage-gated presynaptic Ca2+ channels (CaV) and which is now known to promote the trafficking of the postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) towards the cell membrane. Alterations in CaVγ2 expression has been associated with several neurological disorders, such as absence epilepsy. However, its regulation at the transcriptional level has not been intensively addressed. It has been reported that the promoter of the Cacng2 gene, encoding the rat CaVγ2, is bidirectional and regulates the transcription of a long non-coding RNA (lncRNA) in the antisense direction. Here, we investigate the proximal promoter region of the human CACNG2 gene in the antisense direction and show that this region includes two functional cAMP response elements that regulate the expression of a lncRNA called CACNG2-DT. The activity of these sites is significantly enhanced by forskolin, an adenylate cyclase activator, and inhibited by H89, a protein kinase A (PKA) antagonist. Therefore, this regulatory mechanism implies the activation of G protein-coupled receptors and downstream phosphorylation. Interestingly, we also found that the expression of CACNG2-DT may increase the levels of the CaVγ2 subunit. Together, these data provide novel information on the organization of the human CACNG2-DT gene promoter, describe modulatory domains and mechanisms that can mediate various regulatory inputs, and provide initial information on the molecular mechanisms that regulate the functional expression of the CaVγ2 protein.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Molecular cloning of the gene promoter encoding the human CaVγ2/Stargazin divergent transcript (CACNG2-DT): characterization and regulation by the cAMP-PKA/CREB signaling pathway

Muñoz-Herrera,

Calderón-Rivera,

Zarco

et al. 2023

Front. Physiol.

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“… 10 , 11 , 12 Research has shown that lncRNA plays a key role in the pathogenesis of chronic pain by acting on specific ion channels. 13 However, little is known about the role of ion channel‐related lncRNAs in the prognosis and the regulation of tumor microenvironment (TME) of CC.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the lncRNAs cannot encode proteins, they play key roles in cancer‐related processes by regulating target gene expression 10–12 . Research has shown that lncRNA plays a key role in the pathogenesis of chronic pain by acting on specific ion channels 13 . However, little is known about the role of ion channel‐related lncRNAs in the prognosis and the regulation of tumor microenvironment (TME) of CC.…”

Section: Introductionmentioning

confidence: 99%

Cervical cancer‐specific long non‐coding RNA landscape reveals the favorable prognosis predictive performance of an ion‐channel‐related signature model

Wang,

Zhou

et al. 2024

Cancer Medicine

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BackgroundIon channels play an important role in tumorigenesis and progression of cervical cancer. Multiple long non‐coding RNA genes are widely involved in ion channel‐related signaling regulation. However, the association and potential clinical application of lncRNAs in the prognosis of cervical cancer are still poorly explored.MethodsThirteen patients with cervical cancer were enrolled in current study. Whole transcriptome (involving both mRNAs and lncRNAs) sequencing was performed on fresh tumor and adjacent normal tissues that were surgically resected from patients. A comprehensive cervical cancer‐specific lncRNA landscape was obtained by our custom pipeline. Then, a prognostic scoring model of ion‐channel‐related lncRNAs was established by regression algorithms. The performance of the predictive model as well as its association with the clinical characteristics and tumor microenvironment (TME) status were further evaluated.ResultsTo comprehensively identify cervical cancer‐specific lncRNAs, we sequenced 26 samples of cervical cancer patients and integrated the transcriptomic results. We built a custom analysis pipeline to improve the accuracy of lncRNA identification and functional annotation and obtained 18,482 novel lncRNAs in cervical cancer. Then, 159 ion channel‐ and tumorigenesis‐related (ICTR‐) lncRNAs were identified. Based on nine ICTR‐lncRNAs, we also established a prognostic scoring model and validated its accuracy and robustness in assessing the prognosis of patients with cervical cancer. Besides, the TME was characterized, and we found that B cells, activated CD8+ T, and tertiary lymphoid structures were significantly associated with ICTR‐lncRNAs signature scores.ConclusionWe provided a thorough landscape of cervical cancer‐specific lncRNAs. Through integrative analyses, we identified ion‐channel‐related lncRNAs and established a predictive model for assessing the prognosis of patients with cervical cancer. Meanwhile, we characterized its association with TME status. This study improved our knowledge of the prominent roles of lncRNAs in regulating ion channel in cervical cancer.

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“…Notably, non-coding RNAs (ncRNAs) are altered greatly in both clinical research and pre-clinical models of CP and constitute a regulatory transcriptome network in the pathogenesis of CP ( Ciszek et al, 2015 ; Peng et al, 2017 ; Du et al, 2022 ). Multiple ncRNAs are differentially expressed in the animal models of CP ( Li et al, 2021b ) and are strongly related to various mechanisms, such as pain-related signaling pathways, receptors, cytokines, cell processes, ion channels, and exosomes in cell-to-cell communications ( Wang Z. et al, 2018 ; Xiang et al, 2019 ; Ma et al, 2021 ; Felix et al, 2022 ; Liu et al, 2022 ; Figure 1 ).…”

Section: Introduction and Chronic Pain Overviewmentioning

confidence: 99%

The emerging power and promise of non-coding RNAs in chronic pain

Zhang

Gao

Zhou

et al. 2022

Front. Mol. Neurosci.

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Chronic pain (CP) is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage lasting longer than 3 months. CP is the main reason why people seek medical care and exerts an enormous economic burden. Genome-wide expression analysis has revealed that diverse essential genetic elements are altered in CP patients. Although many possible mechanisms of CP have been revealed, we are still unable to meet all the analgesic needs of patients. In recent years, non-coding RNAs (ncRNAs) have been shown to play essential roles in peripheral neuropathy and axon regeneration, which is associated with CP occurrence and development. Multiple key ncRNAs have been identified in animal models of CP, such as microRNA-30c-5p, ciRS-7, and lncRNA MRAK009713. This review highlights different kinds of ncRNAs in the regulation of CP, which provides a more comprehensive understanding of the pathogenesis of the disease. It mainly focuses on the contributions of miRNAs, circRNAs, and lncRNAs to CP, specifically peripheral neuropathic pain (NP), diabetic NP, central NP associated with spinal cord injury, complex regional pain syndrome, inflammatory pain, and cancer-induced pain. In addition, we summarize some potential ncRNAs as novel biomarkers for CP and its complications. With an in-depth understanding of the mechanism of CP, ncRNAs may provide novel insight into CP and could become new therapeutic targets in the future.

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Ion channel long non-coding RNAs in neuropathic pain

Cited by 6 publications

References 127 publications

Molecular cloning of the gene promoter encoding the human CaVγ2/Stargazin divergent transcript (CACNG2-DT): characterization and regulation by the cAMP-PKA/CREB signaling pathway

Molecular cloning of the gene promoter encoding the human CaVγ2/Stargazin divergent transcript (CACNG2-DT): characterization and regulation by the cAMP-PKA/CREB signaling pathway

Cervical cancer‐specific long non‐coding RNA landscape reveals the favorable prognosis predictive performance of an ion‐channel‐related signature model

The emerging power and promise of non-coding RNAs in chronic pain

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