{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T19:23:42Z","timestamp":1773775422698,"version":"3.50.1"},"reference-count":36,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background and Objective<\/jats:title>\n                    <jats:p>MicroRNAs (miRNAs) are critical regulators of biological processes associated with gastric cancer (GC) progression. Although previous studies have suggested a role for miR-3921 in GC, its function remains unclear. This study investigates the effect of miR-3921 on cell proliferation, migration, and apoptosis in GC, and explores its potential downstream targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The gastric cancer (GC) cell lines, MKN-45 and AGS, were transfected using miR-3921 mimics and inhibitors and the expression of miR-3921 was confirmed by qRT-PCR. The effects of miR-3921 on MKN-45 and AGS cell proliferation, apoptosis and migration were assessed using the CCK-8 assay, flow cytometry, and transwell and wound healing assays, respectively. Bioinformatic analyses based on data from Luciferase reporter assays tested the interaction between miR-3921 and receptor-interacting protein kinase 1 (RIPK1). Western blotting was used to evaluate the regulatory effect of miR-3921 on RIPK1 expression. The Cancer Genome Atlas (TCGA) was employed to assess the expression levels of receptor-interacting protein kinase 1 (RIPK1) in GC versus normal tissues. Survival data were analyzed using datasets obtained from TCGA and the Gene Expression Omnibus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>miR-3921 mimics suppressed proliferation and migration while promoting apoptosis in MKN-45 and AGS cells. The opposite effects were observed using a miR-3921 inhibitor. miR-3921 directly targeted RIPK1 by binding to its 3\u2032-untranslated region (UTR) which downregulated its expression. Furthermore, we observed elevated RIPK1 expression levels in GC tissues compared to normal tissues. Survival analysis indicated varying prognostic significance of RIPK1 across multiple datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>miR-3921 inhibits the progression of GC, and can bind to and regulate RIPK1, indicating that both miR-3921 and RIPK1 may represent potential therapeutic targets in GC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.20850","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:31:02Z","timestamp":1773765062000},"page":"e20850","source":"Crossref","is-referenced-by-count":0,"title":["miR-3921 functions as a tumor suppressor and negatively regulates RIPK1 in gastric cancer"],"prefix":"10.7717","volume":"14","author":[{"given":"Chenguang","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, People\u2019s Hospital of Longhua, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital, University of South China, Hengyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, People\u2019s Hospital of Longhua, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"10.7717\/peerj.20850\/ref-1","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1002\/iub.2259","article-title":"Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression","volume":"72","author":"Ahadi","year":"2020","journal-title":"IUBMB Life"},{"key":"10.7717\/peerj.20850\/ref-2","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.3390\/cancers16091708","article-title":"Prognosis and treatment of gastric cancer: a 2024 update","volume":"16","author":"Burz","year":"2024","journal-title":"Cancer"},{"key":"10.7717\/peerj.20850\/ref-3","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.2147\/ott.S299234","article-title":"MiR-140-3p impedes gastric cancer progression and metastasis by regulating BCL2\/BECN1-mediated autophagy","volume":"14","author":"Chen","year":"2021","journal-title":"OncoTargets and Therapy"},{"key":"10.7717\/peerj.20850\/ref-4","doi-asserted-by":"publisher","first-page":"9714","DOI":"10.1073\/pnas.1901179116","article-title":"Targeting RIPK1 for the treatment of human diseases","volume":"116","author":"Degterev","year":"2019","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.7717\/peerj.20850\/ref-5","doi-asserted-by":"publisher","first-page":"148082","DOI":"10.1016\/j.ijbiomac.2025.148082","article-title":"Polysaccharides of Pseudostellaria heterophylla (Miq.) 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