{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:04:41Z","timestamp":1777723481181,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Innovation System & Education (RISE) pro-gram","award":["2025-RISE-13-WKU"],"award-info":[{"award-number":["2025-RISE-13-WKU"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNAs (miRNAs) play important roles in the regulation of gene expression and are frequently dysregulated in cancer. Among them, the miR-196 family has been implicated in multiple malignancies, including colorectal cancer (CRC), but the isoform-specific transcriptional effects of miR-196A and miR-196B remain poorly understood. In this study, we generated miR-196A and miR-196B knockout SW48 CRC cell lines using CRISPR-based genome editing and performed RNA sequencing to investigate the transcriptional consequences of individual miR-196 isoform deletion. Transcriptomic analysis revealed widespread gene expression changes in both knockout models and demonstrated distinct clustering patterns between parental SW48 cells and miR-196-deficient cells. Functional enrichment analysis indicated that the altered genes were associated with biological processes related to cytoskeletal organization, intracellular transport, protein folding, and metabolic regulation. Notably, both shared and isoform-specific transcriptional alterations were observed, suggesting that miR-196A and miR-196B contribute to partially overlapping but distinct regulatory networks in CRC cells. Collectively, these findings provide a comprehensive transcriptomic overview of miR-196 isoform deletion in colorectal cancer cells and highlight potential isoform-dependent transcriptional programs that may contribute to CRC biology.<\/jats:p>","DOI":"10.3390\/ijms27093959","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:34:42Z","timestamp":1777458882000},"page":"3959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Profiling Reveals Isoform-Specific Regulatory Roles of miR-196A and miR-196B in Colorectal Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Ji Su","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Oral Pharmacology, College of Dentistry, Wonkwang University, Iksan 54538, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Seok","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Oral Pharmacology, College of Dentistry, Wonkwang University, Iksan 54538, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7564-1350","authenticated-orcid":false,"given":"Youn Ho","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Pharmacology, College of Dentistry, Wonkwang University, Iksan 54538, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s11701-026-03332-6","article-title":"Colorectal cancer treatment assisted by robotic platforms\u2014A systematic review","volume":"20","author":"Herbetko","year":"2026","journal-title":"J. Robot. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/ijc.34760","article-title":"Prognostic and predictive impact of metastatic organ involvement on maintenance therapy in advanced metastatic colorectal cancer: Subgroup analysis of patients treated within the PanaMa trial (AIO KRK 0212)","volume":"154","author":"Sommerhauser","year":"2024","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cao, Q., Tian, Y., Deng, Z., Yang, F., and Chen, E. (2024). Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063358"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mukherjee, M., and Goswami, S. (2020). Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV-2. PLoS ONE, 15.","DOI":"10.1101\/2020.06.09.134585"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"154672","DOI":"10.1016\/j.prp.2023.154672","article-title":"Molecular biology of microRNA-342 during tumor progression and invasion","volume":"248","author":"Taghehchian","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18610","DOI":"10.1073\/pnas.0910374106","article-title":"In ovo application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox gene regulation","volume":"106","author":"McGlinn","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/imb.12878","article-title":"Distinct roles of the Hox genes Ultrabithorax and abdominal-A in scorpionfly embryonic proleg development","volume":"33","author":"Liu","year":"2024","journal-title":"Insect Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/jez.b.23118","article-title":"Identification of Hox genes and their expression profiles during embryonic development of the emerging model organism, Macrobrachium olfersii","volume":"338","author":"Jaramillo","year":"2022","journal-title":"J. Exp. Zool. Part B Mol. Dev. Evol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41375-024-02456-8","article-title":"miR-196b-Oct1\/2 axis regulates DNMT3A-mutant AML pathogenesis","volume":"39","author":"Lawler","year":"2025","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155433","DOI":"10.1016\/j.prp.2024.155433","article-title":"miR-196a in the carcinogenesis and other disorders with an especial focus on its biomarker capacity","volume":"260","author":"Khalilian","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s12935-014-0128-2","article-title":"Upregulation of microRNA-196a and microRNA-196b cooperatively correlate with aggressive progression and unfavorable prognosis in patients with colorectal cancer","volume":"14","author":"Ge","year":"2014","journal-title":"Cancer Cell Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13568-025-01869-7","article-title":"Examining miR-196a, miR-196b and NF-kappaBIalpha gene expression in colitis mice model","volume":"15","author":"Rafiezadeh","year":"2025","journal-title":"AMB Express"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.18632\/oncotarget.3066","article-title":"MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells","volume":"6","author":"Mo","year":"2015","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41419-020-02997-7","article-title":"miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling","volume":"11","author":"Huang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.3892\/or.2017.5873","article-title":"Downregulation of microRNA-196a inhibits human liver cancer cell proliferation and invasion by targeting FOXO1","volume":"38","author":"Yang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1582-4934.2010.01219.x","article-title":"MicroRNA-196: Critical roles and clinical applications in development and cancer","volume":"15","author":"Chen","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12935-020-01200-3","article-title":"MicroRNA-196b-5p promotes malignant progression of colorectal cancer by targeting ING5","volume":"20","author":"Xin","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86695","DOI":"10.18632\/oncotarget.13435","article-title":"Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of colorectal cancer","volume":"7","author":"Chen","year":"2016","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1021\/acssynbio.4c00157","article-title":"CRISPR\/Cas9-Based Genome Editing for Protein Expression and Secretion in Kluyveromyces lactis","volume":"13","author":"Liao","year":"2024","journal-title":"ACS Synth. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1093\/nar\/gkx797","article-title":"CRISPR\/Cas9-based genome editing for simultaneous interference with gene expression and protein stability","volume":"45","author":"Martinez","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1021\/acssynbio.1c00516","article-title":"CS-Cells: A CRISPR-Cas12 DNA Device to Generate Chromosome-Shredded Cells for Efficient and Safe Molecular Biomanufacturing","volume":"11","author":"Ali","year":"2022","journal-title":"ACS Synth. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.omto.2022.04.001","article-title":"CRISPR-Cas knockout of miR21 reduces glioma growth","volume":"25","author":"Nieland","year":"2022","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, E.J., Chen, I.H., Kuo, B.Y., Yu, C.C., Lai, M.T., Lin, J.T., Lin, L.Y., Chen, C.M., Hwang, T., and Sheu, J.J. (2022). Alterations of Cytoskeleton Networks in Cell Fate Determination and Cancer Development. Biomolecules, 12.","DOI":"10.3390\/biom12121862"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41392-025-02439-w","article-title":"Navigating the landscape of protein folding and proteostasis: From molecular chaperones to therapeutic innovations","volume":"10","author":"Kuzu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Veyssiere, M., Rodriguez Ordonez, M.D.P., Chalabi, S., Michou, L., Cornelis, F., Boland, A., Olaso, R., Deleuze, J.F., Petit-Teixeira, E., and Chaudru, V. (2024). MYLK*FLNB and DOCK1*LAMA2 gene-gene interactions associated with rheumatoid arthritis in the focal adhesion pathway. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1375036"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Terzi, A., Maqoud, F., Guido, D., Mallardi, D., Aloisio, M., Ura, B., Gualandi, N., Russo, F., and Giannelli, G. (2025). Ion Channel-Extracellular Matrix Interplay in Colorectal Cancer: A Network-Based Approach to Tumor Microenvironment Remodeling. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115147"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1097\/CM9.0000000000002808","article-title":"Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm","volume":"137","author":"Xie","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrc3601","article-title":"A central role for vesicle trafficking in epithelial neoplasia: Intracellular highways to carcinogenesis","volume":"13","author":"Goldenring","year":"2013","journal-title":"Nat. Revs. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1515\/BC.2009.041","article-title":"Flavivirus NS5 associates with host-cell proteins zonula occludens-1 (ZO-1) and regulating synaptic membrane exocytosis-2 (RIMS2) via an internal PDZ binding mechanism","volume":"390","author":"Ellencrona","year":"2009","journal-title":"Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Favara, D.M., Banham, A.H., and Harris, A.L. (2019). ADGRL4\/ELTD1 is a highly conserved angiogenesis-associated orphan adhesion GPCR that emerged with the first vertebrates and comprises 3 evolutionary variants. BMC Evol. Biol., 19.","DOI":"10.1186\/s12862-019-1445-9"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1158\/2159-8290.CD-23-0225","article-title":"The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity","volume":"13","author":"Davies","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0213523","DOI":"10.1128\/aem.02135-23","article-title":"The mitochondrial carboxylase PCCA interacts with Listeria monocytogenes phospholipase PlcB to modulate bacterial survival","volume":"90","author":"Wang","year":"2024","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1007\/s12015-025-10956-y","article-title":"Metabolic Plasticity and Cancer Stem Cell Metabolism: Exploring the Glycolysis-OXPHOS Switch as a Mechanism for Resistance and Tumorigenesis","volume":"21","author":"Keoh","year":"2025","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s10456-012-9279-8","article-title":"The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells","volume":"15","author":"Turtoi","year":"2012","journal-title":"Angiogenesis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00418-008-0435-6","article-title":"The human keratins: Biology and pathology","volume":"129","author":"Moll","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41416-021-01315-y","article-title":"AMD3100\/Plerixafor overcomes immune inhibition by the CXCL12-KRT19 coating on pancreatic and colorectal cancer cells","volume":"125","author":"Fearon","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kuony, A., and Michon, F. (2017). Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00739"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13626","DOI":"10.1038\/s41598-021-92720-z","article-title":"High expression of DNA damage-inducible transcript 4 (DDIT4) is associated with advanced pathological features in the patients with colorectal cancer","volume":"11","author":"Fattahi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/s42003-025-08430-z","article-title":"P300-dependent acetylation of the FOXQ1 complex activates super-enhancers to promote colorectal cancer proliferation and metastasis","volume":"8","author":"Yang","year":"2025","journal-title":"Commun. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3959\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:37:27Z","timestamp":1777459047000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27093959"],"URL":"https:\/\/doi.org\/10.3390\/ijms27093959","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]}}}