{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:04:12Z","timestamp":1784199852443,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171722"],"award-info":[{"award-number":["82171722"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271764"],"award-info":[{"award-number":["82271764"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7212111"],"award-info":[{"award-number":["7212111"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0909900"],"award-info":[{"award-number":["2021YFA0909900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF0714500"],"award-info":[{"award-number":["2023YFF0714500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor\u2010derived exosomes (TDEs) can carry diverse genetic material that modulates pancreatic cancer (PC) proliferation and invasion. Despite this, the involvement of microRNAs (miRNAs) in TDE\u2010mediated tumor progression in PC remains inadequately explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ultracentrifugation was used to isolate exosomes derived from AsPC\u20101 and BxPC\u20103 cells. Cell proliferation was assessed by cell counting kit\u20108 (CCK\u20108) and plate colony formation assays. Cell migration and invasion were evaluated using Transwell assays. Real\u2010time polymerase chain reaction (RT\u2010PCR) was performed to detect the expression levels of miR\u20104644 and Sprouty RTK Signaling Antagonist 3 (SPRY3). A dual\u2010luciferase reporter assay was conducted to verify the binding site between miR\u20104644 and SPRY3. Orthotopic PC xenografts were established to validate the effects of SPRY3 and miR\u20104644. Finally, the relative expression levels of SPRY3 were validated using PC tissue and matched adjacent non\u2010tumor tissue samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MiR\u20104644 was enriched in TDEs, and the inhibition of miR\u20104644 reduced the proliferation, migration, and invasion of PC cells. SPRY3 was identified as a direct target of miR\u20104644, which bound to the 3\u2032\u2010UTR of SPRY3 and suppressed its expression. The inhibitory effects of SPRY3 on PC cell proliferation, migration, and invasion were partially counteracted by miR\u20104644. Importantly, clinical data analysis revealed that SPRY3 expression was significantly downregulated in PC tissues (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Mechanistically, miR\u20104644 targeted SPRY3 and promoted PC cell proliferation, migration, and invasion through the Ras\u2013Raf\u2010MAPK signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MiR\u20104644 is upregulated in PC TDEs and promotes PC cell progression by suppressing SPRY3 expression; high expression of exosomal miR\u20104644 correlates with poor patient prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72000","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T06:55:16Z","timestamp":1780728916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exosomal\n                    <scp>miR<\/scp>\n                    \u20104644 Targets\n                    <scp>SPRY3<\/scp>\n                    to Promote Proliferation and Invasion of Pancreatic Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiangyu","family":"Chu","sequence":"first","affiliation":[{"name":"Department of General Surgery Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases  Beijing China"},{"name":"CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing 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