{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:26Z","timestamp":1760060606661,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cortical transcriptional dysregulation is widespread in Huntington\u2019s disease (HD). We re-examined prefrontal Brodmann Area 9 (BA9) RNA-seq (GSE64810; 20 HD, 49 controls) using BH-FDR and GEO2R to obtain differential-expression statistics for downstream in silico integration. A compact, direction-aware 80-gene panel was assembled for visualization\/ranking only, while inference relied on validated target sets and full-universe testing. At FDR &lt; 0.05, we detected Up = 2923 and Down = 2448 genes (ratio 1.19), indicating a mild predominance of up-regulation. MIR219A2 was strongly down-regulated, and four experimentally validated targets (FOXC1, NFKBIA, SLC38A2, SLC6A20) overlapped the up-regulated core; as expected for n = 4, no GO\/KEGG\/Reactome term met FDR &lt; 0.05, and STRING returned no high-confidence edges. Beyond the curated panel, we tested MIR219A2 (hsa-miR-219a-5p; hsa-miR-219a-1-3p; hsa-miR-219a-2-3p) targets against the full FDR-significant BA9 up-regulated universe. Two orthogonal, experimentally supported resources\u2014miRTarBase functional assays and ENCORI\/starBase CLIP\u2014showed direction-consistent, FDR-controlled enrichment, with effect sizes and uncertainty reported in the main text, supporting a BA9-specific, MIR219A2-aligned association signal. On the TF axis, MSigDB C3:TFT (gene symbols) revealed significant over-representation of TF target sets among BA9-Up under the same BA9 expressed-gene background after BH-FDR (e.g., NFAT motifs, C\/EBP, FOXA\/HNF3), while TRRUST v2 applied to the MIR219A2 CLIP\u2013BA9-Up subset provided target-level transparency. MIR219A2 enrichments were robust to composition sensitivity analyses (marker-excluded and neuron\/glia-stratified backgrounds). Exploratory GO\u2013Biological Process bubbles are shown for trend summarization only; no term met FDR &lt; 0.05 in the primary analysis. All conclusions are analysis-only; no wet-lab or biofluid\/peripheral assays were performed, and findings are BA9-specific\u2014generalization to other regions remains hypothesis-generating.<\/jats:p>","DOI":"10.3390\/ijms26188934","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T07:33:02Z","timestamp":1758007982000},"page":"8934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BA9 Transcriptomics in Huntington\u2019s Disease 80-Gene Signature and MIR219A2-Linked Targets"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-1834","authenticated-orcid":false,"given":"G\u00f6zde","family":"\u00d6ztan","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Topkap\u0131, 34093 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-706X","authenticated-orcid":false,"given":"Halim","family":"\u0130\u015fsever","sequence":"additional","affiliation":[{"name":"Department of Public Health, Istanbul Faculty of Medicine, Istanbul University, Topkap\u0131, 34093 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Levent","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Labor Economics and Industrial Relations, Faculty of Economics, Istanbul University, Fatih, 34126 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Huntington\u2019s Disease Collaborative Research Group (1993). 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