{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:53:33Z","timestamp":1776664413559,"version":"3.51.2"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Protein tyrosine phosphatase non-receptor type 12 (PTPN12), a crucial enzymatic protein involved in cellular signaling, remains understudied in colorectal cancer (CRC). This study investigates this biological macromolecule\u2019s potential as a biomarker, examining its protein-protein interactions, therapeutic relevance, and immunomodulatory functions in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a comprehensive analysis of PTPN12 using public datasets and clinical samples. Bioinformatics tools were employed to predict regulators and signaling pathways associated with PTPN12. Immune infiltration analysis and re-analysis of publicly available single-cell RNA sequencing (scRNA-seq) datasets were performed to explore the immunomodulatory role of PTPN12. The relationship between PTPN12 protein levels and drug susceptibility was evaluated. Functional assays validated PTPN12\u2019s role in CRC cells and its impact on oxaliplatin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PTPN12 protein is significantly upregulated in CRC tissues, with its elevated expression correlating with poor prognosis. PTPN12 correlates with increased genomic instability. PTPN12 is involved in various biological processes, including the regulation of cellular and developmental processes. Furthermore, high PTPN12 expression is positively correlated with stromal cell infiltration, suggesting a potential role in modulating the immune response. These findings collectively suggest that PTPN12 may have potential as a therapeutic candidate and immunotherapy-related biomarker. Knockdown of PTPN12 inhibited CRC cell proliferation, migration, and invasion. Notably, PTPN12 protein was overexpressed in oxaliplatin-resistant CRC cells, and its inhibition restored chemosensitivity in in vitro models.\u200b<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PTPN12 shows promise as a potential biomarker and therapeutic target candidate in CRC. Our study provides preliminary insights into the role of PTPN12 in CRC pathogenesis, treatment response, and chemoresistance, which may lay the groundwork for future development of personalized therapeutic strategies pending further\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1766515","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:24:32Z","timestamp":1776662672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PTPN12 is a novel biomarker associated with genomic instability, therapeutic potentials, and immunomodulator in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Siyi","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, China"]},{"name":"Department of Histology and Embryology, Xiangya School of Basic Medical Sciences, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peihe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of anesthesiology, Third Xiangya hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Xiangya School of Basic Medical Sciences, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1111\/febs.13600","article-title":"The extended human PTPome: a growing tyrosine phosphatase family","volume":"283","author":"Alonso","year":"2016","journal-title":"FEBS J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.3390\/cells11091502","article-title":"Crocin inhibits angiogenesis and metastasis in Colon cancer via TNF-alpha\/NF-kB\/VEGF pathways","volume":"11","author":"Bakshi","year":"2022","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1002\/humu.24057","article-title":"Candidate genes for hereditary colorectal cancer: mutational screening and systematic review","volume":"41","author":"Belhadj","year":"2020","journal-title":"Hum. 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