{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:43:14Z","timestamp":1785825794154,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>Circular RNAs (circRNAs), a novel RNA type generated by back\u2010splicing, are key regulators of gene expression, with deregulated expression and established involvement in leukemia. The products of <jats:italic>BCL2<\/jats:italic> and its homologs, including <jats:italic>BAX<\/jats:italic> and <jats:italic>BCL2L12<\/jats:italic>, are implicated in chronic lymphocytic leukemia (CLL). However, to the best of our knowledge, nothing is known about circRNAs produced by these two genes and their role in CLL. We sought to further elucidate the contribution of <jats:italic>BAX<\/jats:italic> and <jats:italic>BCL2L12<\/jats:italic> in CLL by unraveling the identity, localization, and potential role of their circRNAs. Therefore, total RNA from the EHEB cell line and peripheral blood mononuclear cells (PBMCs) of CLL patients and non\u2010leukemic blood donors was extracted and reverse\u2010transcribed using random hexamers. Next, nested PCRs with divergent primers were performed and the purified PCR products were subjected to 3rd generation nanopore sequencing. Nested PCRs were also applied to first\u2010strand cDNAs synthesized from total RNA extracts of PBMCs from CLL patients and non\u2010leukemic blood donors. Lastly, a single\u2010molecule resolution fluorescent <jats:italic>in\u2009situ<\/jats:italic> hybridization method called circFISH was used to visualize the circRNA distribution in EHEB cells. We discovered several novel circRNAs produced by <jats:italic>BAX<\/jats:italic> and <jats:italic>BCL2L12<\/jats:italic>, which were characterized by great exon structure diversity. In addition, intriguing findings regarding their formation emerged. Interestingly, visualization of the most abundant circRNAs showed distinct intracellular localization. Moreover, a complex <jats:italic>BAX<\/jats:italic> and <jats:italic>BCL2L12<\/jats:italic> circRNA expression pattern was revealed in CLL patients and non\u2010leukemic blood donors. Our data suggest a multifaceted role of <jats:italic>BAX<\/jats:italic> and <jats:italic>BCL2L12<\/jats:italic> circRNAs in B\u2010cell CLL.<\/jats:p>","DOI":"10.1002\/2211-5463.13672","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T08:10:47Z","timestamp":1688976647000},"page":"1953-1966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel circular <scp>RNAs<\/scp> of the apoptosis\u2010related <i>BAX<\/i> and <i>BCL2L12<\/i> genes identified in a chronic lymphocytic leukemia cell line using nanopore sequencing"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9935-8461","authenticated-orcid":false,"given":"Christos K.","family":"Kontos","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology National and Kapodistrian University of Athens  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