{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:25:19Z","timestamp":1787574319213,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science, Research and Innovation Fund"},{"DOI":"10.13039\/501100004508","name":"Prince of Songkla University","doi-asserted-by":"publisher","award":["SCI6901266S"],"award-info":[{"award-number":["SCI6901266S"]}],"id":[{"id":"10.13039\/501100004508","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004508","name":"Prince of Songkla University","doi-asserted-by":"publisher","award":["1-2567-02-022"],"award-info":[{"award-number":["1-2567-02-022"]}],"id":[{"id":"10.13039\/501100004508","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SCI6901266S"],"award-info":[{"award-number":["SCI6901266S"]}],"id":[{"id":"https:\/\/ror.org\/0575ycz84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1-2567-02-022"],"award-info":[{"award-number":["1-2567-02-022"]}],"id":[{"id":"https:\/\/ror.org\/0575ycz84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is an aggressive malignancy with limited treatment options and poor clinical outcomes. Kinesin light chain 1 (KLC1), a component of the kinesin-1 motor complex involved in intracellular transport, has been implicated in cancer biology; however, its role in CCA remains unclear. This study investigated the functional role and molecular alterations associated with KLC1 silencing in CCA. Analysis of publicly available datasets showed that KLC1 mRNA expression was significantly elevated in CCA tissues, and immunohistochemical images from the Human Protein Atlas demonstrated stronger KLC1 protein expression in tumor tissues. siRNA-mediated KLC1 knockdown markedly suppressed cell proliferation, migration, and invasion in KKU-213A and KKU-055 cells and altered the expression of epithelial\u2013mesenchymal transition-associated proteins. Transcriptomic profiling identified 2074 differentially expressed genes following KLC1 knockdown. Functional enrichment analyses revealed significant alterations in cytoskeleton-associated processes and mitogen-activated protein kinase (MAPK) signaling. Protein\u2013protein interaction network analysis identified interconnected gene networks associated with these pathways. Selected differentially expressed genes were validated by RT\u2013qPCR, supporting the transcriptomic findings. Collectively, these results suggest that KLC1 contributes to aggressive phenotypes in CCA cells and is associated with transcriptomic alterations involving cytoskeletal regulation and MAPK signaling, highlighting KLC1 as a potential contributor to CCA progression and warranting further investigation.<\/jats:p>","DOI":"10.3390\/ijms27177525","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"7525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silencing of Kinesin Light Chain 1 Suppresses Aggressive Phenotypes in Cholangiocarcinoma Cells Through Transcriptomic Alterations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4928-2643","authenticated-orcid":false,"given":"Thanakrit","family":"Rattanaarchanai","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phonprapavee","family":"Tantimetta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6800-1048","authenticated-orcid":false,"given":"Phanthipha","family":"Runsaeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-7917","authenticated-orcid":false,"given":"Sompop","family":"Saeheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-0563","authenticated-orcid":false,"given":"Sumalee","family":"Obchoei","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"},{"name":"Center of Excellence for Biochemistry, Faculty of Science, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41575-025-01153-w","article-title":"Cholangiocarcinoma 2026: Status quo, unmet needs and priorities","volume":"23","author":"Banales","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"Brindley","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.pt.2024.10.012","article-title":"Mechanistic insights into liver-fluke-induced bile-duct cancer","volume":"40","author":"Smout","year":"2024","journal-title":"Trends Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/jgh.70208","article-title":"Systemic Therapy for Advanced Biliary Tract Cancers in 2026: Current Standard of Care and Emerging Therapeutic Strategies","volume":"41","author":"Yoon","year":"2026","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Khosla, D., Misra, S., Chu, P.L., Guan, P., Nada, R., Gupta, R., Kaewnarin, K., Ko, T.K., Heng, H.L., and Srinivasalu, V.K. (2024). Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches. Cancers, 16.","DOI":"10.3390\/cancers16040801"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.21037\/jgo-22-1126","article-title":"The novel epithelial-mesenchymal transition-related proteins and their therapeutic targets in cholangiocarcinoma: A narrative review","volume":"14","author":"Kimawaha","year":"2023","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nrm2774","article-title":"Kinesin superfamily motor proteins and intracellular transport","volume":"10","author":"Hirokawa","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41419-018-0549-2","article-title":"Kinesin light chain-4 depletion induces apoptosis of radioresistant cancer cells by mitochondrial dysfunction via calcium ion influx","volume":"9","author":"Baek","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s12032-025-03044-1","article-title":"Kinesin superfamily proteins in ovarian cancer: From molecular mechanisms to clinical applications","volume":"42","author":"Bishoyi","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12031-025-02308-9","article-title":"Decoding the Role of Kinesin Superfamily Proteins in Glioma Progression","volume":"75","author":"Saadh","year":"2025","journal-title":"J. Mol. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22946","DOI":"10.1074\/jbc.M212160200","article-title":"A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1","volume":"278","author":"Inomata","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1091\/mbc.e06-02-0112","article-title":"Calsyntenin-1 docks vesicular cargo to kinesin-1","volume":"17","author":"Konecna","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38601","DOI":"10.1074\/jbc.M304379200","article-title":"Amyloid \u03b2 protein precursor (A\u03b2PP), but not A\u03b2PP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1","volume":"278","author":"Matsuda","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1242\/jcs.075168","article-title":"Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1","volume":"124","author":"Vagnoni","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/1759-7714.14886","article-title":"The kinesin light chain-2, a target of mRNA stabilizing protein HuR, inhibits p53 protein phosphorylation to promote radioresistance in NSCLC","volume":"14","author":"Qiao","year":"2023","journal-title":"Thorac. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/bjc.2015.3","article-title":"High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients","volume":"112","author":"Wang","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3892\/or.2025.8900","article-title":"KLC3 activates PI3K\/AKT signaling and promotes ovarian cancer cell proliferation and migration through COL3A1","volume":"53","author":"Yang","year":"2025","journal-title":"Oncol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41419-020-2592-z","article-title":"Kinesin light chain 4 as a new target for lung cancer chemoresistance via targeted inhibition of checkpoint kinases in the DNA repair network","volume":"11","author":"Baek","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/1759-7714.12613","article-title":"ALK-rearrangement in non-small-cell lung cancer (NSCLC)","volume":"9","author":"Du","year":"2018","journal-title":"Thorac. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Togashi, Y., Soda, M., Sakata, S., Sugawara, E., Hatano, S., Asaka, R., Nakajima, T., Mano, H., and Takeuchi, K. (2012). KLC1-ALK: A novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031323"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ebiom.2019.06.009","article-title":"A role for kinesin-1 subunits KIF5B\/KLC1 in regulating epithelial mesenchymal plasticity in breast tumorigenesis","volume":"45","author":"Moamer","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kerdkumthong, K., Nanarong, S., Roytrakul, S., Pitakpornpreecha, T., Tantimetta, P., Runsaeng, P., and Obchoei, S. (2024). Quantitative proteomics analysis reveals possible anticancer mechanisms of 5\u2032-deoxy-5\u2032-methylthioadenosine in cholangiocarcinoma cells. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0306060"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhong, M., Gong, L., Li, N., Guan, H., Gong, K., Zhong, Y., Zhu, E., Wang, X., Jiang, S., and Li, J. (2023). Pan-cancer analysis of kinesin family members with potential implications in prognosis and immunological role in human cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1179897"},{"key":"ref_24","first-page":"10","article-title":"Biological Features of KLC2 Mutations in Chronic Myeloid Leukemia and Their Contribution to Inducing Drug Resistance","volume":"34","author":"Bera","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30185","DOI":"10.1074\/jbc.M505499200","article-title":"JLP associates with kinesin light chain 1 through a novel leucine zipper-like domain","volume":"280","author":"Nguyen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13946","DOI":"10.1074\/jbc.RA118.003916","article-title":"Characterization of the binding mode of JNK-interacting protein 1 (JIP1) to kinesin-light chain 1 (KLC1)","volume":"293","author":"Nguyen","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s12033-025-01428-2","article-title":"From Motor Proteins to Oncogenic Factors: The Evolving Role of Kinesin Superfamily Proteins in Breast Cancer Development","volume":"68","author":"Saadh","year":"2026","journal-title":"Mol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115621","DOI":"10.1016\/j.intimp.2025.115621","article-title":"Kinesin superfamily proteins in cancer: Unveiling their role in chemotherapy","volume":"166","author":"Owida","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1038\/onc.2011.437","article-title":"Lemur tyrosine kinase-2 signalling regulates kinesin-1 light chain-2 phosphorylation and binding of Smad2 cargo","volume":"31","author":"Manser","year":"2012","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.21037\/tlcr-23-482","article-title":"Primary resistance to ALK inhibitors in KLC1\/ALK-rearranged pleural metastatic lung adenocarcinoma: A case report","volume":"12","author":"Siblini","year":"2023","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.20892\/j.issn.2095-3941.2017.0017","article-title":"Rapid response of brain metastasis to crizotinib in a patient with KLC1-ALK fusion and MET gene amplification positive non-small cell lung cancer: A case report","volume":"14","author":"Wang","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","article-title":"UALCAN: An update to the integrated cancer data analysis platform","volume":"25","author":"Chandrashekar","year":"2022","journal-title":"Neoplasia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7525\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:52:12Z","timestamp":1787572332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":35,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177525"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177525","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]}}}