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Integrated Transcriptomic Analysis Identifies a Putative cfa-miR-10a-ACTG1/SDC1 Network Associated with Extracellular
Mohammad Arif1,2, Most Shumi Akhter Shathi1, Nobuhiro Nozaki1
1Joint Graduate School of Veterinary Medicine, Kagoshima University, Kagoshima 890-8580, Japan.
Abstract:
A coordinated extracellular matrix (ECM) and cytoskeletal remodeling are critical drivers of hepatocellular carcinoma (HCC) progression, yet the upstream post-transcriptional mechanisms regulating these processes in spontaneous canine HCC remain poorly defined. Previously, we reported significantly downregulated miRNAs and enriched pathways from differentially expressed genes (DEGs) in canine HCC tissues. In the present study, we investigated putative post-transcriptional target interactions between the prioritized miRNAs and enriched ECM-cytoskeleton pathway-associated genes (n = 34). Integrative bioinformatic analysis prioritized ACTG1 and SDC1 as the key putative targets of cfa-miR-10a based on their concordant prediction by four target-prediction algorithms, high transcript abundance, and inverse correlations with cfa-miR-10a-5p. RNAhybrid and miRanda analyses supported favorable predicted interactions between cfa-miR-10a and the 3'UTRs of both transcripts, with RNAhybrid minimum free energy values ≤ -20 kcal/mol and miRanda scores ≥ 140. In the matched canine transcriptomic subset, cfa-miR-10a and its predicted targets showed inverse expression trends. Cross-species analysis using TCGA-LIHC datasets further demonstrated concordant dysregulation of ACTG1, SDC1 and hsa-miR-10a-5p in human HCC, despite their weak or non-concordant correlation with hsa-miR-10a-5p. Collectively, these exploratory findings identify a candidate cfa-miR-10a-ACTG1/SDC1 network associated with coordinated ECM and cytoskeletal transcriptomic alterations in canine HCC. While cross-species analysis supports the conservation of target gene dysregulation, the divergent miRNA-mRNA correlation patterns highlight potential species-specific post-transcriptional co-expression landscapes that warrant future functional validation.

