{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:27:50Z","timestamp":1783794470495,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health Research Institutes","award":["CA-111-PP-13"],"award-info":[{"award-number":["CA-111-PP-13"]}]},{"name":"National Health Research Institutes","award":["CA-112-PP-13"],"award-info":[{"award-number":["CA-112-PP-13"]}]},{"name":"National Health Research Institutes","award":["CA-113-PP-13"],"award-info":[{"award-number":["CA-113-PP-13"]}]},{"name":"National Health Research Institutes","award":["MOST111-2314-B-400-029-MY3"],"award-info":[{"award-number":["MOST111-2314-B-400-029-MY3"]}]},{"name":"National Science and Technology Council","award":["CA-111-PP-13"],"award-info":[{"award-number":["CA-111-PP-13"]}]},{"name":"National Science and Technology Council","award":["CA-112-PP-13"],"award-info":[{"award-number":["CA-112-PP-13"]}]},{"name":"National Science and Technology Council","award":["CA-113-PP-13"],"award-info":[{"award-number":["CA-113-PP-13"]}]},{"name":"National Science and Technology Council","award":["MOST111-2314-B-400-029-MY3"],"award-info":[{"award-number":["MOST111-2314-B-400-029-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metastasis is a well-known factor worsening colorectal cancer (CRC) prognosis, but mortality mechanisms in non-metastatic patients with poor outcomes are less understood. TCF12 is a transcription factor that can be physically associated with the long non-coding RNA MALAT1, creating an alliance with correlated expression levels in CRC patients. This TCF12\u2013MALAT1 alliance is linked to poorer prognosis independently of age and metastasis. To identify the downstream effects responsible for this outcome, we analyzed 2312 common target genes of TCF12 and MALAT1, finding involvement in pathways like Aurora B, ATM, PLK1, and non-canonical WNT. We investigated the impact of WNT downstream genes CTNNB1 and CCND1, encoding \u03b2-catenin and cyclin D1, respectively, on survival in CRC patients with this alliance. Tumors with higher TCF12 and MALAT1 gene expressions alongside increased \u03b2-catenin gene expressions were classified as having a \u201cPan-CMS-2 pattern\u201d, showing relatively better prognoses. Conversely, tumors with high TCF12, MALAT1, and cyclin D1 gene expressions but low \u03b2-catenin expression were categorized as \u201cTMBC pattern\u201d, associated with poor survival, with survival rates dropping sharply from 60% at one year to 30% at three years. This suggests that targeting cyclin D1-associated CDK4\/6 could potentially reduce early mortality risks in TMBC patients, supporting personalized medicine approaches.<\/jats:p>","DOI":"10.3390\/cells13242035","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:15:03Z","timestamp":1733804103000},"page":"2035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TCF12 and LncRNA MALAT1 Cooperatively Harness High Cyclin D1 but Low \u03b2-Catenin Gene Expression to Exacerbate Colorectal Cancer Prognosis Independently of Metastasis"],"prefix":"10.3390","volume":"13","author":[{"given":"Chia-Ming","family":"Wu","sequence":"first","affiliation":[{"name":"Graduate Program of Biotechnology in Medicine, National Health Research Institutes, National Tsing Hua University, Hsinchu City 300, Taiwan"},{"name":"Institute of Biotechnology, National Tsing Hua University, Hsinchu City 300, Taiwan"},{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-7368","authenticated-orcid":false,"given":"Chung-Hsing","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"},{"name":"Department of Mathematics, University of Taipei, Taipei City 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9028-9834","authenticated-orcid":false,"given":"Kuo-Wang","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Yu","family":"Tsai","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shone","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9570-3611","authenticated-orcid":false,"given":"Horng-Dar","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Program of Biotechnology in Medicine, National Health Research Institutes, National Tsing Hua University, Hsinchu City 300, Taiwan"},{"name":"Institute of Biotechnology, National Tsing Hua University, Hsinchu City 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-4330","authenticated-orcid":false,"given":"Tze-Sing","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Program of Biotechnology in Medicine, National Health Research Institutes, National Tsing Hua University, Hsinchu City 300, Taiwan"},{"name":"National Institute of Cancer Research, National Health Research Institutes, Miaoli County 350, Taiwan"},{"name":"Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan"},{"name":"Doctoral Program in Tissue Engineering and Regenerative Medicine, Biotechnology Center, National Chung Hsing University, Taichung City 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1093\/nar\/19.16.4555","article-title":"HTF4, a new human helix-loop-helix protein","volume":"19","author":"Zhang","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_2","first-page":"1031","article-title":"HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA binding ability of myogenic regulatory factors","volume":"12","author":"Hu","year":"1992","journal-title":"Mol. 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