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. 2023 Oct;60(10):5672-5690.
doi: 10.1007/s12035-023-03398-5. Epub 2023 Jun 19.

Transcriptome Profiling of miRNA-mRNA Interactions and Associated Mechanisms in Chemotherapy-Induced Neuropathic Pain

Xiaohua Yang #  1 , Xiqiang Huang #  2 , Weicheng Lu #  1 , Fang Yan  1 , Yaqi Ye  1 , Linjie Wang  3 , Xiaole Tang  1 , Weian Zeng  1 , Jingxiu Huang  4 , Jingdun Xie  5
Affiliations

Transcriptome Profiling of miRNA-mRNA Interactions and Associated Mechanisms in Chemotherapy-Induced Neuropathic Pain

Xiaohua Yang et al. Mol Neurobiol. 2023 Oct.

Abstract

Chemotherapy-induced neuropathic pain (CINP) is a dose-limiting adverse event affecting 40% of chemotherapy patients. MiRNA-mRNA interaction plays an important role in various processes. However, detailed profiling of miRNA-mRNA interactions in CINP remains unclear. Here, a rat-based CINP model was established using paclitaxel, followed by nociceptive behavioral tests related to mechanical allodynia, thermal hyperalgesia, and cold allodynia. The landscape of miRNA-mRNA interaction in the spinal dorsal horn was investigated through mRNA transcriptomics and small RNA sequencing. Under CINP condition, 86 differentially expressed mRNAs and 56 miRNAs were identified. Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated the activity of Odorant binding, postsynaptic specialization and synaptic density, extracellular matrix, mitochondrial matrix, retrograde endocannabinoid signaling, and GTPase activity. Protein-protein interaction (PPI), networks of circRNA-miRNA-mRNA, lncRNA-miRNA-mRNA, and TF-genes were demonstrated. We next explored the immune infiltration microenvironment and found a higher infiltration abundance of Th17 and a lower abundance of MDSC in CINP. RT-qPCR and dual-luciferase assays were used to verify the sequencing results, and single-cell analysis based on the SekSeeq database was conducted. Combined with bioinformatics analyses and experimental validations, Mpz, a protein-coding gene specifically expressed in Schwann cells, was found critical in maintaining CINP under miRNA regulation. Therefore, these data highlight the expression patterns of miRNA-mRNA, and the underlying mechanism in the spinal dorsal horn under CINP condition, and Mpz may serve as a promising therapeutic target for patients with CINP.

Keywords: Chemotherapy-induced neuropathic pain; Immune microenvironment; Mpz; Small RNA sequencing; Transcriptomics sequencing; ceRNA.

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References

    1. Staff NP, Grisold A, Grisold W, Windebank AJ (2017) Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol 81(6):772–781. https://doi.org/10.1002/ana.24951 - DOI - PubMed - PMC
    1. Gornstein E, Schwarz TL (2014) The paradox of paclitaxel neurotoxicity: mechanisms and unanswered questions. Neuropharmacology 76(Pt A):175–183. https://doi.org/10.1016/j.neuropharm.2013.08.016 - DOI - PubMed
    1. Pease-Raissi SE, Pazyra-Murphy MF, Li Y, Wachter F, Fukuda Y, Fenstermacher SJ, Barclay LA, Bird GH, Walensky LD, Segal RA (2017) Paclitaxel reduces axonal bclw to initiate IP3R1-dependent axon degeneration. Neuron 96(2):373–38. https://doi.org/10.1016/j.neuron.2017.09.034
    1. Zhang J, Pan Y, Shi Q, Zhang G, Jiang L, Dong X, Gu K, Wang H, Zhang X, Yang N, Li Y, Xiong J, Yi T, Peng M, Song Y, Fan Y, Cui J, Chen G, Tan W, Zang A, Guo Q, Zhao G, Wang Z, He J, Yao W, Wu X, Chen K, Hu X, Hu C, Yue L, Jiang D, Wang G, Liu J, Yu G, Li J, Bai J, Xie W, Zhao W, Wu L, Zhou C (2022) Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study. Cancer Commun (Lond) 42(1):3–16. https://doi.org/10.1002/cac2.12225
    1. Rodwin RL, Kairalla JA, Hibbitts E, Devidas M, Whitley MK, Mohrmann CE, Schore RJ, Raetz E et al (2022) Persistence of chemotherapy-induced peripheral neuropathy despite vincristine reduction in childhood B-acute lymphoblastic leukemia. J Natl Cancer Inst 114(8):1167–1175. https://doi.org/10.1093/jnci/djac095 - DOI - PubMed - PMC

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