{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:45:30Z","timestamp":1781901930237,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project of the Liaoning Provincial Department of Education","award":["LZ2019060"],"award-info":[{"award-number":["LZ2019060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Despite advancements in diagnostic efficiency, colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with increasing incidence rates. Circular RNA (circRNA) is a closed-loop, generally stable noncoding RNA that functions as a sponge for microRNAs in CRC. The purpose of this study was to investigate the function and underlying mechanism of circ_RUSC2, a new circRNA, in CRC. The expression levels of circ_RUSC2, miR-661, and TUSC2 were assessed using qRT-PCR, Western blot, and immunohistochemistry. Functional assays, including CCK-8, Transwell, and scratch wound healing, were performed to evaluate cell proliferation, migration, and invasion. RNA pull-down and actinomycin D assays were used to study RNA interactions and stability. In both CRC cells and tissues, miR-661 was markedly elevated, while circ_RUSC2 expression was considerably reduced. Poor differentiation, distant metastases, lymph node metastases, and an advanced stage were all strongly correlated with either miR-661 overexpression or circ_RUSC2 downregulation. circ_RUSC2 was more stable compared to its linear RUSC2 mRNA. CRC cell invasion, migration, and proliferation were suppressed by circ_RUSC2 ectopic expression; this inhibitory effect was restored by a miR-661 mimic. Circ_RUSC2 served as miR-661\u2019s sponge. TUSC2 counteracted the effects of miR-661, which stimulated CRC cell proliferation, migration, and invasion. At the post-transcriptional level, miR-661 controlled the expression of TUSC2 in CRC cells. In comparison to the negative control, circ_RUSC2 expression was markedly reduced, and its half-life was shortened by methyltransferase-like 3 (METTL3) knockdown. Circ_RUSC2 is a stable cytoplasmic circRNA. Circ_RUSC2 inhibits CRC cell malignant phenotypes via the miR-661\/TUSC2 axis. The onset and progression of CRC are linked to the downregulation of Circ_RUSC2. circ_RUSC2 might become more stable through N6-methyladenosine (m6A) methylation regulated by METTL3. According to our research, circ_RUSC2 might be a new biomarker and treatment target for CRC.<\/jats:p>","DOI":"10.3390\/ijms26072937","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:01:50Z","timestamp":1742817710000},"page":"2937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circ_RUSC2 Sequesters miR-661 and Elevates TUSC2 Expression to Suppress Colorectal Cancer Progression"],"prefix":"10.3390","volume":"26","author":[{"given":"Yixin","family":"Shi","sequence":"first","affiliation":[{"name":"Liaoning Laboratory of Cancer Genomics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingru","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510641, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Psychology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Guo","sequence":"additional","affiliation":[{"name":"Liaoning Laboratory of Cancer Genomics, Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Medical Morphology Laboratory, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8035-5682","authenticated-orcid":false,"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medical Morphology Laboratory, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2323861","DOI":"10.1080\/21645515.2024.2323861","article-title":"Mapping the intellectual structure and landscape of colorectal cancer immunotherapy: A bibliometric analysis","volume":"20","author":"Ou","year":"2024","journal-title":"Hum. 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