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Acupuncture is an effective therapeutic intervention, yet its underlying molecular mechanisms remain incompletely elucidated. To evaluate the clinical efficacy of acupuncture for PFP and to identify differentially expressed RNAs and associated pathways via whole transcriptome analysis, thereby revealing potential molecular mechanisms. Clinical efficacy was assessed using the House-Brackmann (HB) scale, Facial Disability Index (FDI), and comprehensive traditional Chinese medicine efficacy criteria. Peripheral blood samples were collected from patients before and after acupuncture treatment. Differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs were screened through whole transcriptome sequencing. Bioinformatics analyses were employed to construct a competing endogenous RNA (ceRNA) network and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Acupuncture significantly improved clinical scores post-treatment. A total of 1625 differentially expressed mRNAs (1153 up-, 472 down-regulated), 715 lncRNAs (321 up-, 394 down-regulated), 85 circRNAs (56 up-, 29 down-regulated), and 253 miRNAs (141 up-, 112 down-regulated) were identified. The ceRNA network revealed that non-coding RNAs competitively bind key miRNA molecules, forming two distinct and independent regulatory axes that precisely modulate downstream target genes. KEGG enrichment analysis of core molecular targets indicated significant involvement in the Olfactory transduction and JAK-STAT signaling pathways. Acupuncture may exert its therapeutic effect on PFP by modulating the ceRNA network, alongside the Olfactory transduction and JAK-STAT signaling pathways, synergistically promoting nerve regeneration and suppressing neuroinflammation.<\/jats:p>","DOI":"10.1007\/s12031-026-02599-6","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:34:25Z","timestamp":1791668065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Transcriptomic Analysis Identifies Potential Biomarkers and Underlying Mechanisms of Acupuncture in Treating Peripheral Facial Paralysis"],"prefix":"10.1007","volume":"76","author":[{"given":"Xihong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runyu","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"issue":"12","key":"2599_CR1","doi-asserted-by":"publisher","first-page":"e0278509","DOI":"10.1371\/journal.pone.0278509","volume":"17","author":"Y Zhou","year":"2022","unstructured":"Zhou Y, Huang G, Luo C et al (2022) Efficacy and safety of electric acupuncture in treatment of intractable facial paralysis: A protocol for systematic review and meta-analysis. 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