{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:07:44Z","timestamp":1779084464272,"version":"3.51.4"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Adoptive cellular immunotherapy (ACT) such as CAR\u2011T therapy holds promise for cancer treatment. However, genetically engineered T cells often undergo terminal differentiation during ex vivo expansion, which limits their persistence and antitumor efficacy\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Early\u2011differentiated T\u2011cell subsets exhibit better survival and proliferative capacity after infusion. In our previous work, we isolated four T\u2011cell subsets at different differentiation stages: na\u00efve T cells (T\n                      <jats:sub>N<\/jats:sub>\n                      ), stem cell\u2011like memory T cells (TSCM), central memory T cells (T\n                      <jats:sub>CM<\/jats:sub>\n                      ), and\u00a0effector memory T cells (T\n                      <jats:sub>EM<\/jats:sub>\n                      ), and obtained their miRNA expression profiles\u00a0via\u00a0high\u2011throughput sequencing. In the present study, we found that hsa\u2011miR\u2011142\u20115p is highly expressed in TSCM cells and gradually decreases during T\u2011cell differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Bioinformatics analysis suggested that miR\u2011142\u20115p target genes are involved in transcription regulation. We identified four candidate targets through reverse enrichment analysis. Dual\u2011luciferase reporter assays were used to validate direct targets. Functional studies were then performed in T cells overexpressing miR\u2011142\u20115p to assess expression of differentiation\u2011associated and effector\u2011related genes, surface markers (CCR7, CD62L, CD95), cell subset proportions (T\n                      <jats:sub>N<\/jats:sub>\n                      , T\n                      <jats:sub>SCM<\/jats:sub>\n                      , T\n                      <jats:sub>EM<\/jats:sub>\n                      \/T\n                      <jats:sub>EFF<\/jats:sub>\n                      ), proliferation, apoptosis, and cytokine secretion (TNF\u2011\u03b1, IFN\u2011\u03b3).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dual\u2011luciferase reporter assays confirmed PRKCB as a direct target of miR\u2011142\u20115p, and miR\u2011142\u20115p suppressed PRKCB expression in T cells. miR\u2011142\u20115p overexpression upregulated early differentiation\u2011associated genes (LEF1, CD62L, CCR7) and the anti\u2011apoptotic gene BCL2, while downregulating late differentiation\u2011associated genes (KLRG1, EOMES, PDCD1) and effector function\u2011related genes (GZMB, PRF1). Consistently, it enhanced early differentiation markers (CCR7, CD62L) and reduced the late marker CD95. It also increased T\n                      <jats:sub>N<\/jats:sub>\n                      and T\n                      <jats:sub>SCM<\/jats:sub>\n                      proportions while decreasing T\n                      <jats:sub>EM<\/jats:sub>\n                      \/T\n                      <jats:sub>EFF<\/jats:sub>\n                      cells. Additionally, miR\u2011142\u20115p promoted T\u2011cell proliferation, reduced apoptosis, and suppressed TNF\u2011\u03b1 and IFN\u2011\u03b3 secretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In summary, miR\u2011142\u20115p inhibits progressive T\u2011cell differentiation by directly targeting PRKCB, helping maintain an early\u2011differentiated phenotype. This offers a potential strategy to improve the persistence and efficacy of adoptive T\u2011cell\u2011based immunotherapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1807053","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:42:09Z","timestamp":1779082929000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-142-5p promotes TSCM differentiation and suppresses progressive T-cell maturation via targeting PRKCB"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongqiong","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengfang","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Science and Education Division, Public Health Clinical Center of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huishan","family":"Zhong","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianpei","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zitao","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangdong Pharmaceutical University","place":["Guangzhou, Guangdong, 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