{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:02:03Z","timestamp":1784678523612,"version":"3.55.0"},"reference-count":58,"publisher":"Institution of Engineering and Technology (IET)","issue":"1","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":201,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ietresearch.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IET Systems Biology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is a major cause of cancer\u2010related death worldwide. Although the nucleolar protein NOL12 has been implicated in HCC progression, its comprehensive expression patterns, clinical significance and regulation\u2014particularly the potential involvement of miR\u20101246\u20105p and H3K27ac\u2014are not fully understood, warranting further investigation. To analyse the expression pattern and clinical significance of NOL12, we integrated bulk RNA sequencing (bulk RNA\u2010seq) data (4264 HCC cases vs. 3145 non\u2010HCC cases), single\u2010cell RNA sequencing (scRNA\u2010seq) data (12 HCC samples) and spatial transcriptomics (ST) data from public databases including GEO, TCGA and GTEx. This integration was combined with in\u2010house immunohistochemistry (IHC) data from 394 pairs of HCC tissues and adjacent non\u2010tumour tissues. CRISPR screening was used to assess the effect of NOL12 depletion on HCC cell proliferation. Seven immune infiltration analysis methods (including CIBERSORT) were applied to the TCGA\u2010GTEx dataset to explore the association between NOL12 and the tumour immune microenvironment (TME). Gene ontology (GO) enrichment, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment Analysis (GSEA) were performed based on NOL12\u2010associated genes involved in HCC initiation and progression. Additionally, chromatin immunoprecipitation sequencing (ChIP\u2010seq) data from Cistrome DB were used to predict and construct the miR\u20101246\u20105p\u2013enhancer\u2013NOL12 regulatory network. Potential high\u2010affinity drug molecules targeting NOL12 were screened via the Cancer Therapeutics Response Portal (CTRP) database and molecular docking. Multi\u2010dimensional analysis revealed significant upregulation of NOL12 in HCC (SMD\u00a0=\u00a00.64, 95% CI: 0.42\u20130.85; sROC AUC\u00a0=\u00a00.79). IHC validation confirmed higher NOL12 expression in HCC tissues (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001, ROC AUC\u00a0=\u00a00.665). CRISPR screening showed that NOL12 depletion inhibited HCC cell proliferation. Mechanistically, NOL12 was enriched in the spliceosome pathway. ChIP\u2010seq identified an H3K27ac\u2010modified enhancer in the NOL12 promoter overlapping with miR\u20101246\u20105p binding sites, and miR\u20101246\u20105p expression positively correlated with NOL12 (\n                    <jats:italic>r<\/jats:italic>\n                    \u00a0=\u00a00.43,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.018). Drug sensitivity prediction analysis showed that NOL12 protein exhibited significant sensitivity to BRD\u2010K71781559, MST\u2010312, IU1, BRD9876 and PRL\u20103 inhibitor I, with favourable binding energies. NOL12 may be regulated by the putative miR\u20101246\u20105p\/H3K27ac enhancer axis and promotes HCC progression through the spliceosome pathway, supporting its potential as a novel therapeutic target for HCC.\n                  <\/jats:p>","DOI":"10.1049\/syb2.70071","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:22:49Z","timestamp":1784676169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Potential miR\u20101246\u20105p\u2013H3K27ac\u2013NOL12 Regulatory Axis and Its Putative Tumour\u2010Promoting Function in Hepatocellular Carcinoma"],"prefix":"10.1049","volume":"20","author":[{"given":"Li","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Long","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Na","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"},{"name":"Department of Pathology Wuming Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Di","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong\u2010Quan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Tong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathology Yulin Red Cross Hospital  Yulin 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