{"title":"PDCD4 interacting with PIK3CB and CTSZ promotes the apoptosis of multiple myeloma cells","authors":"Liyuan Liu, Xiumei Feng, Chenliu Fan, Dexiao Kong, Xiaoli Feng, Chenxi Sun, Yaqi Xu, Binggen Li, Yang Jiang, Chengyun Zheng","doi":"10.1096/fj.202400687R","DOIUrl":null,"url":null,"abstract":"<p>The role of programmed cell death 4 (PDCD4) in multiple myeloma (MM) development remains unknown. Here, we investigated its role and action mechanism in MM. Bioinformatic analysis indicated that patients with MM and high PDCD4 expression had higher overall survival than those with low PDCD4 expression. PDCD4 expression promoted MM cell apoptosis and inhibited their viability in vitro and tumor growth in vivo. RNA-binding protein immunoprecipitation sequencing analysis showed that PDCD4 is bound to the 5′ UTR of the apoptosis-related genes <i>PIK3CB</i>, Cathepsin Z (<i>CTSZ</i>), and X-chromosome-linked apoptosis inhibitor (<i>XIAP</i>). <i>PDCD4</i> knockdown reduced the cell apoptosis rate, which was rescued by adding PIK3CB, CTSZ, or XIAP inhibitors. Dual luciferase reporter assays confirmed the internal ribosome entry site (IRES) activity of the 5′ UTRs of <i>PIK3CB</i> and <i>CTSZ</i>. An RNA pull-down assay confirmed binding of the 5′ UTR of <i>PIK3CB</i> and <i>CTSZ</i> to PDCD4, identifying the specific binding fragments. PDCD4 is expected to promote MM cell apoptosis by binding to the IRES domain in the 5′ UTR of <i>PIK3CB</i> and <i>CTSZ</i> and inhibiting their translation. Our findings suggest that PDCD4 plays an important role in MM development by regulating the expression of P<i>IK3CB</i>, <i>CTSZ,</i> and <i>XIAP</i>, and highlight new potential molecular targets for MM treatment.</p>","PeriodicalId":50455,"journal":{"name":"FASEB Journal","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1096/fj.202400687R","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The role of programmed cell death 4 (PDCD4) in multiple myeloma (MM) development remains unknown. Here, we investigated its role and action mechanism in MM. Bioinformatic analysis indicated that patients with MM and high PDCD4 expression had higher overall survival than those with low PDCD4 expression. PDCD4 expression promoted MM cell apoptosis and inhibited their viability in vitro and tumor growth in vivo. RNA-binding protein immunoprecipitation sequencing analysis showed that PDCD4 is bound to the 5′ UTR of the apoptosis-related genes PIK3CB, Cathepsin Z (CTSZ), and X-chromosome-linked apoptosis inhibitor (XIAP). PDCD4 knockdown reduced the cell apoptosis rate, which was rescued by adding PIK3CB, CTSZ, or XIAP inhibitors. Dual luciferase reporter assays confirmed the internal ribosome entry site (IRES) activity of the 5′ UTRs of PIK3CB and CTSZ. An RNA pull-down assay confirmed binding of the 5′ UTR of PIK3CB and CTSZ to PDCD4, identifying the specific binding fragments. PDCD4 is expected to promote MM cell apoptosis by binding to the IRES domain in the 5′ UTR of PIK3CB and CTSZ and inhibiting their translation. Our findings suggest that PDCD4 plays an important role in MM development by regulating the expression of PIK3CB, CTSZ, and XIAP, and highlight new potential molecular targets for MM treatment.
期刊介绍:
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.