Mechanistic Study of LAMP-2A/TRIM23 in the Occurrence and Development of Pancreatic Cancer

Mechanistic Study of LAMP-2A/TRIM23 in the Occurrence and Development of Pancreatic Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mechanistic Study of LAMP-2A/TRIM23 in the Occurrence and Development of Pancreatic Cancer Chunxiu Tan, Ying Yang, Yuanzhen Wang, Jia Wu, Liya Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9342538/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Objective Pancreatic adenocarcinoma (PAAD) is a highly malignant digestive tract tumor with an extremely poor prognosis. The chaperone-mediated autophagy (CMA) core receptor LAMP-2A and the E3 ubiquitin ligase TRIM23 have attracted increasing attention for their roles in tumorigenesis, progression, and the regulation of tumor-associated macrophages (TAMs). However, their functions in PAAD remain insufficiently studied. Therefore, this study aims to investigate the roles of LAMP-2A/TRIM23 in PAAD tumorigenesis and the tumor microenvironment, and to preliminarily explore their mechanisms of action. Methods The expression and prognostic value of LAMP-2A and TRIM23 were assessed through bioinformatics analysis and validation in clinical PAAD tissues.Their functions in tumor cell proliferation, migration, and invasion were evaluated in vitro via Transwell assays following gene knockdown or overexpression.A subcutaneous xenograft mouse model and a macrophage-tumor cell co-culture system (using THP-1-derived macrophages) were established.The impact of LAMP-2A/TRIM23 on M1/M2 polarization of TAMs was analyzed by Western blotting, quantitative PCR, and ELISA. Results LAMP-2A and TRIM23 were significantly overexpressed in PAAD tissues, and high expression of either gene correlated with poor patient survival. Functionally, knockdown of either LAMP-2A or TRIM23 inhibited pancreatic cancer cell proliferation, migration, and invasion in vitro, and suppressed subcutaneous tumor growth in vivo, whereas overexpression of LAMP-2A promoted these malignant phenotypes.Mechanistically, not only knockdown in macrophages but also knockdown in pancreatic cancer cells themselves effectively reprogrammed co-cultured TAMs from a tumor-promoting M2 phenotype toward an anti-tumor M1 phenotype. Conclusion LAMP-2A and TRIM23 are upregulated in PAAD and cooperatively drive tumor progression by modulating the tumor immune microenvironment via promoting M2 macrophage polarization. Pancreatic Cancer LAMP-2A TRIM23 Tumor Associated Macrophages Tumor Microenvironment Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 13 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 03 May, 2026 Reviewers agreed at journal 30 Apr, 2026 Reviews received at journal 30 Apr, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviews received at journal 27 Apr, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviewers invited by journal 20 Apr, 2026 Editor invited by journal 20 Apr, 2026 Editor assigned by journal 18 Apr, 2026 Submission checks completed at journal 17 Apr, 2026 First submitted to journal 17 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9342538","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":631239109,"identity":"02b2b254-3700-4bb5-b387-29271230c461","order_by":0,"name":"Chunxiu Tan","email":"","orcid":"","institution":"Ningxia Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chunxiu","middleName":"","lastName":"Tan","suffix":""},{"id":631239110,"identity":"7066f414-c3f2-441a-8e09-6c288721383e","order_by":1,"name":"Ying Yang","email":"","orcid":"","institution":"Ningxia Medical University General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Yang","suffix":""},{"id":631239111,"identity":"2c678e85-a5d9-42a6-80a9-89425df01e86","order_by":2,"name":"Yuanzhen Wang","email":"","orcid":"","institution":"Ningxia Medical University General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanzhen","middleName":"","lastName":"Wang","suffix":""},{"id":631239112,"identity":"305e7de2-dec2-4b8b-b02f-a486f64319c4","order_by":3,"name":"Jia Wu","email":"","orcid":"","institution":"Ningxia Medical University General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Wu","suffix":""},{"id":631239113,"identity":"86fa4429-3524-4814-a666-241194675b23","order_by":4,"name":"Liya Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAnElEQVRIiWNgGAWjYHACNgaGCgk5fqLV84C1nLEwlmwgSQtjW0XiBqK12Etkpz3mnSfBuIGB+eGjG0TZwnN2uzHvNglmcwY2Y+McorSw926Tzt0mwWbZwMMmTZwWZl6gljkSPAYHiNYCtqVBQoIELWeAfvlzTMJAsplYv7DPyN32cEZNXX0/e/PDx0RpQQBm0pSPglEwCkbBKMAHACx1KOyM3UUOAAAAAElFTkSuQmCC","orcid":"","institution":"Ningxia Medical University General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Liya","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2026-04-07 09:23:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9342538/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9342538/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108182210,"identity":"c9d20d35-ad3d-48e3-852a-169cd27e26a1","added_by":"auto","created_at":"2026-04-30 08:59:15","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2694135,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9342538/v1_covered_6d8dfd36-16d2-4c2e-ac23-bf7eaf2da621.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mechanistic Study of LAMP-2A/TRIM23 in the Occurrence and Development of Pancreatic Cancer","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pancreatic Cancer, LAMP-2A, TRIM23, Tumor Associated Macrophages, Tumor Microenvironment","lastPublishedDoi":"10.21203/rs.3.rs-9342538/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9342538/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003ePancreatic adenocarcinoma (PAAD) is a highly malignant digestive tract tumor with an extremely poor prognosis. The chaperone-mediated autophagy (CMA) core receptor LAMP-2A and the E3 ubiquitin ligase TRIM23 have attracted increasing attention for their roles in tumorigenesis, progression, and the regulation of tumor-associated macrophages (TAMs). However, their functions in PAAD remain insufficiently studied. Therefore, this study aims to investigate the roles of LAMP-2A/TRIM23 in PAAD tumorigenesis and the tumor microenvironment, and to preliminarily explore their mechanisms of action.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe expression and prognostic value of LAMP-2A and TRIM23 were assessed through bioinformatics analysis and validation in clinical PAAD tissues.Their functions in tumor cell proliferation, migration, and invasion were evaluated in vitro via Transwell assays following gene knockdown or overexpression.A subcutaneous xenograft mouse model and a macrophage-tumor cell co-culture system (using THP-1-derived macrophages) were established.The impact of LAMP-2A/TRIM23 on M1/M2 polarization of TAMs was analyzed by Western blotting, quantitative PCR, and ELISA.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eLAMP-2A and TRIM23 were significantly overexpressed in PAAD tissues, and high expression of either gene correlated with poor patient survival. Functionally, knockdown of either LAMP-2A or TRIM23 inhibited pancreatic cancer cell proliferation, migration, and invasion in vitro, and suppressed subcutaneous tumor growth in vivo, whereas overexpression of LAMP-2A promoted these malignant phenotypes.Mechanistically, not only knockdown in macrophages but also knockdown in pancreatic cancer cells themselves effectively reprogrammed co-cultured TAMs from a tumor-promoting M2 phenotype toward an anti-tumor M1 phenotype.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLAMP-2A and TRIM23 are upregulated in PAAD and cooperatively drive tumor progression by modulating the tumor immune microenvironment via promoting M2 macrophage polarization.\u003c/p\u003e","manuscriptTitle":"Mechanistic Study of LAMP-2A/TRIM23 in the Occurrence and Development of Pancreatic Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-29 15:28:04","doi":"10.21203/rs.3.rs-9342538/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-13T14:26:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T16:34:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13452173915438008596553083505585387622","date":"2026-05-03T20:09:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267909460508702791111259480169122316386","date":"2026-04-30T13:32:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T08:11:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"203901341222722068333550372994419697695","date":"2026-04-30T00:30:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-27T20:17:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267061280224452973528052255008584475924","date":"2026-04-27T20:05:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-20T17:39:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-20T17:27:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-18T06:07:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-17T05:49:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-04-17T05:42:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"01e54d16-7fd6-4007-ae86-298da988e82f","owner":[],"postedDate":"April 29th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-13T14:26:07+00:00","index":47,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T16:34:00+00:00","index":45,"fulltext":""},{"type":"reviewerAgreed","content":"13452173915438008596553083505585387622","date":"2026-05-03T20:09:12+00:00","index":44,"fulltext":""},{"type":"reviewerAgreed","content":"267909460508702791111259480169122316386","date":"2026-04-30T13:32:25+00:00","index":42,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T08:11:34+00:00","index":41,"fulltext":""},{"type":"reviewerAgreed","content":"203901341222722068333550372994419697695","date":"2026-04-30T00:30:59+00:00","index":40,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-29T15:28:05+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-29 15:28:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9342538","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9342538","identity":"rs-9342538","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}