{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T22:33:02Z","timestamp":1775773982746,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"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. Cell Dev. Biol."],"abstract":"<jats:p>Mounting evidence has demonstrated that circular RNAs have an important function in tumorigenesis and cancer evolvement. CircCRIM1 has been shown to be a poor prognostic element in multiple human malignancies. However, the clinical significance and mechanism of circCRIM1 in hepatocellular carcinoma (HCC) is still unclear. The present study confirmed the expression level of circCRIM1 using quantitative real-time PCR. In addition, circCRIM1 siRNA and overexpression vectors were used for transfection into LM3 or Huh7 cells to down- or up-regulate the expression of circCRIM1. <jats:italic>In vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments were performed to explore the function of circCRIM1 in HCC. RNA pull-down, RNA immunoprecipitation, fluorescent <jats:italic>in situ<\/jats:italic> hybridization, and luciferase reporter assays were conducted to confirm the relationship between miR-378a-3p and circCRIM1 or S-phase kinase-associated protein 2 (SKP2) in HCC. Then, circCRIM1 was up-regulated in HCC and its expression level was significantly associated with poor prognosis and clinicopathologic characteristics. CircCRIM1 enhanced the proliferation and angiogenesis of HCC cells <jats:italic>in vitro<\/jats:italic> and promoted xenograft growth <jats:italic>in vivo<\/jats:italic>. Moreover, circCRIM1 upregulated the expression of SKP2 by functioning as a sponge for miR-378a-3p. These findings suggest that circCRIM1 boosts the HCC progression via the miR-378-3p\/SKP2 axis and may act as a crucial epigenetic therapeutic molecule target in HCC.<\/jats:p>","DOI":"10.3389\/fcell.2021.796686","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T07:08:35Z","timestamp":1636700915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["CircCRIM1 Promotes Hepatocellular Carcinoma Proliferation and Angiogenesis by Sponging miR-378a-3p and Regulating SKP2 Expression"],"prefix":"10.3389","volume":"9","author":[{"given":"Yang","family":"Ji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shikun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinchen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longqing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunjie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/S0140-6736(17)33326-3","article-title":"Global Surveillance of Trends in Cancer Survival 2000-14 (CONCORD-3): Analysis of Individual Records for 37\u2008513\u2008025 Patients Diagnosed with One of 18 Cancers from 322 Population-Based Registries in 71 Countries","volume":"391","author":"Allemani","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.2147\/CMAR.S289826","article-title":"A Prognostic Scoring System for Predicting Overall Survival of Patients with the TNM 8th Edition Stage I and II Hepatocellular Carcinoma after Surgery: A Population-Based Study","volume":"13","author":"Bai","year":"2021","journal-title":"Cmar"},{"key":"B3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/cac2.12025","article-title":"Cancer burden of Major Cancers in China: A Need for Sustainable Actions","volume":"40","author":"Cao","year":"2020","journal-title":"Cancer Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s12943-020-01272-9","article-title":"The Circular RNA Circ-ERBIN Promotes Growth and Metastasis of Colorectal Cancer by miR-125a-5p and miR-138-5p\/4EBP-1 Mediated Cap-independent HIF-1\u03b1 Translation","volume":"19","author":"Chen","year":"2020","journal-title":"Mol. 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