{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:51:09Z","timestamp":1782449469830,"version":"3.54.5"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Multiple myeloma (MM) is incurable and many patients respond poorly to bortezomib. New strategies to improve bortezomib sensitivity are needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We screened bortezomib-responsive miRNAs by RNA-seq in RPMI8226 cells (fold change &amp;gt;4, P&amp;lt;0.05). miR-1248 was measured by qRT-PCR in MM cells and in plasma from 30 patients before\/after VCD therapy. MEF2C was examined by qRT-PCR and Western blot. A dual-luciferase reporter assay was performed to test miR-1248 binding to the MEF2C 3\u2032-UTR. After miR-1248 inhibitor transfection, we detected MEF2C, p38 and autophagy markers by qRT-PCR\/Western blot and assessed autophagic activity by staining. Rescue experiments overexpressed MEF2C.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , a xenograft model (n=6) was used to detect these markers after miR-1248 inhibition plus bortezomib(0.5 mg\/kg).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bortezomib increased miR-1248 by 2-fold (P&amp;lt;0.05) and reduced MEF2C mRNA by 62% and protein by 55% (both P&amp;lt;0.01). Plasma miR-1248 also rose after VCD therapy (median 2.1-fold, P&amp;lt;0.05). Luciferase assays confirmed direct targeting of the MEF2C 3\u2032-UTR by miR-1248. Inhibiting miR-1248 reduced bortezomib-induced autophagy markers and staining, and partially restored MEF2C and p38 (P&amp;lt;0.05). MEF2C overexpression weakened bortezomib-induced apoptosis (cell viability rose from 42\u00a0\u00b1\u00a05% to 71\u00a0\u00b1\u00a06%, P&amp;lt;0.01) and suppressed those markers. In xenografts, miR-1248 knockdown cut tumor inhibition from 58\u00a0\u00b1\u00a07% to 23\u00a0\u00b1\u00a09% (P&amp;lt;0.01), with partial restoration of MEF2C\/p38 and blunted autophagy marker elevation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that miR-1248 enhances bortezomib sensitivity in MM cells by directly targeting MEF2C, accompanied by reduced p38 expression and autophagic activity. The coordinated changes in MEF2C and p38 define a functional axis that may be targeted to improve bortezomib response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1847922","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:37:43Z","timestamp":1782448663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-1248 enhances bortezomib-induced autophagy by targeting MEF2C\/p38-MAPK signaling in multiple myeloma"],"prefix":"10.3389","volume":"16","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Chengde Medical College","place":["Chengde, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Chengde Medical 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