Sarah A Dooley, Rachel Stubler, Priti Parsanna Maity, Jorge Múnera, Antonis Kourtidis, Melinda A Engevik, Amy C Engevik
{"title":"The molecular motor Myosin 5B and its folding chaperone UNC45A are decreased in colorectal cancer.","authors":"Sarah A Dooley, Rachel Stubler, Priti Parsanna Maity, Jorge Múnera, Antonis Kourtidis, Melinda A Engevik, Amy C Engevik","doi":"10.1016/j.jcmgh.2025.101537","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer ranks among the most common and deadliest cancers worldwide. Previous studies have found that the molecular motor Mysoin 5b (MYO5B) is decreased at the level of mRNA in colorectal cancer, but the mechanism behind this reduction remains unknown. In normal cells, MYO5B function is contingent on proper folding by the chaperone protein UNC45A. However, little is known about the role of UNC45A in colorectal cancer.</p><p><strong>Methods: </strong>We examined RNA, methylation and protein levels of MYO5B and UNC45A and identified microRNAs targeting UNC45A in normal colon, colon adenocarcinoma (COAD) samples, cancer cell lines and human colonic organoids. Cells were treated with the DNA-demethylating agent 5-aza-2'-deoxycytidine to examine the role of methylation in regulating MYO5B levels. Additionally, the UNC45A targeting miR-296-3p was inhibited in cells and UNC45A levels were examined.</p><p><strong>Results: </strong>Consistent with previous reports, we found that MYO5B mRNA was reduced in COAD compared to controls. We observed that the MYO5B gene was hyper-methylated in COAD and treatment of cancer cells with a demethylating compound increased MYO5B expression; suggesting that methylation silences MYO5B in COAD. The MYO5B folding chaperone UNC45A was not changed at the mRNA level but was decreased at the protein level. We identified several UNC45A targeting miRNAs which were elevated in COAD patients. We confirmed that these miRNAs were elevated in colon cancer cell lines compared to normal colonic organoids and found that inhibition of one of these miRNAs increased UNC45A protein.</p><p><strong>Conclusions: </strong>These findings suggest that decreased levels of MYO5B in COAD may result from gene methylation and improper folding by UNC45A.</p>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101537"},"PeriodicalIF":7.1000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Gastroenterology and Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jcmgh.2025.101537","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Colorectal cancer ranks among the most common and deadliest cancers worldwide. Previous studies have found that the molecular motor Mysoin 5b (MYO5B) is decreased at the level of mRNA in colorectal cancer, but the mechanism behind this reduction remains unknown. In normal cells, MYO5B function is contingent on proper folding by the chaperone protein UNC45A. However, little is known about the role of UNC45A in colorectal cancer.
Methods: We examined RNA, methylation and protein levels of MYO5B and UNC45A and identified microRNAs targeting UNC45A in normal colon, colon adenocarcinoma (COAD) samples, cancer cell lines and human colonic organoids. Cells were treated with the DNA-demethylating agent 5-aza-2'-deoxycytidine to examine the role of methylation in regulating MYO5B levels. Additionally, the UNC45A targeting miR-296-3p was inhibited in cells and UNC45A levels were examined.
Results: Consistent with previous reports, we found that MYO5B mRNA was reduced in COAD compared to controls. We observed that the MYO5B gene was hyper-methylated in COAD and treatment of cancer cells with a demethylating compound increased MYO5B expression; suggesting that methylation silences MYO5B in COAD. The MYO5B folding chaperone UNC45A was not changed at the mRNA level but was decreased at the protein level. We identified several UNC45A targeting miRNAs which were elevated in COAD patients. We confirmed that these miRNAs were elevated in colon cancer cell lines compared to normal colonic organoids and found that inhibition of one of these miRNAs increased UNC45A protein.
Conclusions: These findings suggest that decreased levels of MYO5B in COAD may result from gene methylation and improper folding by UNC45A.
期刊介绍：
"Cell and Molecular Gastroenterology and Hepatology (CMGH)" is a journal dedicated to advancing the understanding of digestive biology through impactful research that spans the spectrum of normal gastrointestinal, hepatic, and pancreatic functions, as well as their pathologies. The journal's mission is to publish high-quality, hypothesis-driven studies that offer mechanistic novelty and are methodologically robust, covering a wide range of themes in gastroenterology, hepatology, and pancreatology.
CMGH reports on the latest scientific advances in cell biology, immunology, physiology, microbiology, genetics, and neurobiology related to gastrointestinal, hepatobiliary, and pancreatic health and disease. The research published in CMGH is designed to address significant questions in the field, utilizing a variety of experimental approaches, including in vitro models, patient-derived tissues or cells, and animal models. This multifaceted approach enables the journal to contribute to both fundamental discoveries and their translation into clinical applications, ultimately aiming to improve patient care and treatment outcomes in digestive health.
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