miRNA-193a acts as a tumor suppressor in human head and neck cancer cells and inhibits tumor development in xenograft mice

miRNA-193a acts as a tumor suppressor in human head and neck cancer cells and inhibits tumor development in xenograft mice | 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 Article miRNA-193a acts as a tumor suppressor in human head and neck cancer cells and inhibits tumor development in xenograft mice Fuad Fares, Reem Miari, Naiel Azzam, Rinat Bar Shalom, Tina Napso, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4310591/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract miRNAs are small non-coding RNA molecules, involved in the regulation of gene expression via binding to messenger RNA (mRNA), thereby preventing protein translation. We found that the promotor region of miR-193a is highly methylated in FaDu head and neck cancer cells, assuming that its expression is suppressed. Moreover, our results indicated that miRNA-193a levels are undetectable in biopsies of head and neck cancer patients. Induction of miR-193a expression by treatment with methyltransferase inhibitor or transduction of head and neck squamous cell carcinoma (HNSCC) cells with miR-193a resulted in a significant decrease in cell viability in a dose and time-dependent manners, as well as induction of apoptosis through the caspase intrinsic pathway. Moreover, miR-193a also inhibited tumour growth in xenograft mice transplanted with FaDu cells. In addition, we found that miR-193a inactivates the AKT/mTOR signaling pathway through the downregulation of PIK3R3, mTOR, S6KB2, and ERBB4. These observations suggest that miR-193a plays an important role in tumor biogenesis and therefore has the potential to serve for diagnostics as well as therapeutics in HNSCC. Biological sciences/Cancer Biological sciences/Cancer/Cancer therapy/Targeted therapies Health sciences/Biomarkers/Diagnostic markers Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Full Text Additional Declarations (Not answered) Supplementary Files ERBB4.pdf OriginalGels.pdf PIK3R3.pdf S6KB2.pdf mTOR.pdf Cite Share Download PDF Status: Posted Version 1 posted 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-4310591","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":306325169,"identity":"6deb943a-a55d-4f2b-8810-80576789d92d","order_by":0,"name":"Fuad Fares","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIie3RMQrCMBSA4ScP0iXF9TmoV6gExEH0Ki2Cs+AqUhHqpLPeQnEQt0hBNz2AkwjOBUEcithWERyaOjrkJyQk8NG0BdDp/jBjKOOlDoDJoPzr3KqlEr6146X9IQX3RSiL+MkmIvAmoCAML0EQHpyVwS3s9GqUd/EUQEdFmJjNvKOzHkZkuiUiyQSpLtYsuwJN9+jMfWYjZ9QHCVX1uzDjimG4f5MHUVkatwzCBQKTEUGJpkdkSZ71FN7Njb2WiIlvTogqPu+Srb7YEu5hozg/bAZnfutTaTdaRN+wnkq+kskc/x37N6DT6XS6lJ6wNkYha5f/0QAAAABJRU5ErkJggg==","orcid":"","institution":"University of Haifa","correspondingAuthor":true,"prefix":"","firstName":"Fuad","middleName":"","lastName":"Fares","suffix":""},{"id":306325170,"identity":"137756f3-ce36-47c3-9997-76a155cd6b0e","order_by":1,"name":"Reem Miari","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Reem","middleName":"","lastName":"Miari","suffix":""},{"id":306325171,"identity":"4d4e92ba-7d3b-4456-8541-19477ca3cfd6","order_by":2,"name":"Naiel Azzam","email":"","orcid":"https://orcid.org/0000-0001-5717-7972","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Naiel","middleName":"","lastName":"Azzam","suffix":""},{"id":306325172,"identity":"07ac01be-d552-402e-ae31-6284c3ee79a0","order_by":3,"name":"Rinat Bar Shalom","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Rinat","middleName":"Bar","lastName":"Shalom","suffix":""},{"id":306325173,"identity":"0b1f72bc-4c5b-4ee1-87b8-a4ccf0b1a0db","order_by":4,"name":"Tina Napso","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tina","middleName":"","lastName":"Napso","suffix":""},{"id":306325174,"identity":"93d6c4c8-0455-48db-9455-23f2382a1e16","order_by":5,"name":"Ohad Ronen","email":"","orcid":"https://orcid.org/0000-0001-7084-0695","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ohad","middleName":"","lastName":"Ronen","suffix":""}],"badges":[],"createdAt":"2024-04-23 08:47:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4310591/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4310591/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58077236,"identity":"0223b4eb-c80e-4cdb-b7b7-56131b4c011b","added_by":"auto","created_at":"2024-06-10 22:30:45","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":541022,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) \u003c/strong\u003eSchematic representation of the CMV-GFP-miR-193a-5p expression cassette inserted into the AD-CMV-miR-193a-5p vector backbone. \u003cstrong\u003e(B) \u003c/strong\u003eSchematic view of the AD-5 backbone plasmid pAdeno-miR193a-GFP expression cassette.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/81613f1d08cd487ebfa26666.jpg"},{"id":58077237,"identity":"f3e9e6d9-b5e7-4020-806a-38843f4d6807","added_by":"auto","created_at":"2024-06-10 22:30:45","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":715761,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA Methylation profile of miRNA-193 in Fadu cells. \u003c/strong\u003e(A) miRNA-193a showed high levels of methylation rate on the promotor region in the squamous cell carcinoma of the hypopharynx originated cell line (Fadu) compared to the tongue originated cells (SCC-9 and SCC-25) and to normal fibroblasts. The expression levels of miRNA-193a were analyzed using Quantitative real-time PCR, following 5-aza-2`-deoxycytidine cell treatment or following Ad-miR-193a transduction. (B) Data represented are the average of three independent experiments conducted in triplicates (mean ± SD). U6 was used for normalization. Statistical significance determined by a two-tailed Student's t-test. Significance was determined as follows: *** P\u0026lt;0.001.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/57da432adb12653b0f29484e.jpg"},{"id":58076871,"identity":"723b7d1b-f0f7-4f9c-ac36-6cf0f27d0006","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":795200,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\n\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCell viability following Ad-miR-193a transduction. \u003c/strong\u003e(A) FaDu cells were transduced with three different working concentrations of AD-miR-193a viral vector. Cell viability was determined 48h post transduction. The presented data are means ± SD of three experiments, each conducted in eight replicates, and are expressed as percentages of the respective control (*** P\u0026lt;0.001, ** P\u0026lt;0.01 (Dunnett's test). (B) FaDu cells were transduced with 5X10\u003csup\u003e9\u003c/sup\u003e pfu/ml of AD-miR-193a viral vector. Cell viability was determined 24h, 48h and 72h post transduction. Data presented are means ± SD of three experiments, each conducted in eight replicates, and are expressed as percentages of the respective control. Statistical significance determined by a two-tailed student's t-test. *** P\u0026lt;0.001. (C) Analysis of cell cycle distribution. 1x10\u003csup\u003e6\u003c/sup\u003e FaDu cells were implanted into six well plates. 24 hours later cells were transduced with either Ad -GFP vector (control group) or Ad-miR-193a vector at 10\u003csup\u003e10\u003c/sup\u003e vp/well concentration for 48 hours. Cells were then harvested, fixed and stained with PI and subjected to a cell cycle analysis using FACS Calibur. The distribution and percentage of cells in the Sub-G1 phase of the cell cycle are presented. A is a representative histogram of three experiments. (D) Average percentage of the cells in Sub-G1 and G2M from 3-5 independent experiments repeats each (cells were pooled before staining). Statistical significance was determined (**P\u0026lt;0.01Dunnett's test).\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/e9f7810cba42d1ea9dc4fd59.jpg"},{"id":58076870,"identity":"9c54af89-79e7-4dd8-ab96-1ab19078be7e","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":770827,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEvaluation of apoptosis rate following transduction of FaDu cells with Ad-miR-193a using Annexin V binding, TUNEL assay and detection of apoptosis markers. \u003c/strong\u003eFaDu cells were transduced with A-miR-193 for a period of 24 and 48 hours. Control cells were transduced with Adeno-GFP. (A) Detection of apoptotic cells by Flow cytometric analysis of annexin V-FITC/PI double-stained . (B) Detection of apoptotic cells by TUNEL assay following treatment of the cells with Ad-193a for 48h. Blue-colored cells (DAPI dye) are living cells; red colored cells (fluorescence-labeled dUTP) are apoptotic cells. (C) Western blot analysis of apoptotic markers following transduction of FaDu cells with Ad-miR-193a. Cells were transduced with 5X10\u003csup\u003e9\u003c/sup\u003e pfu/ml Ad-miR -193 or 5X10\u003csup\u003e9\u003c/sup\u003e pfu/ml Ad-GFP for control. 24 and 48-hours following transduction, total protein was extracted. Equal amounts of protein samples (50 jig) were separated on 12% SDS-PAGE and exposed to specific antibody; Cytochrome C, caspase 8,caspase-9, caspase 3, PARP or \u003cem\u003eβ\u003c/em\u003e-Actine. Statistical significance determined by a two-tailed student's t-test [treatment vs. control (untreated cells)] and is indicated as **p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/b40636aa78c3857114818282.jpg"},{"id":58076873,"identity":"ccc33268-975f-4f0e-910a-75249efb0747","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":565161,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression levels of PIK3R3, S6KB2, mTOR, and ERBB4 in FaDu cells following Ad-miR-193a transduction. \u003c/strong\u003emRNA levels of PIK3R3 (A), S6KB2 (B), mTOR (C) and ERBB4 (D) were measured using qRT–PCR. FaDu cells were transduced with Ad-miR-193a or Ad-GFP for the control. 48 hours following transduction, the expression levels of mRNA were separately quantified using TaqMan expression assays (as described under Materials and Methods) and normalized using HBRT as internal expression control. Significant statistical differences were observed between the control and the treatment.\u003c/p\u003e\n\u003cp\u003eThe data are representative average of three independent experiments +SD (***P\u0026lt;0.001 by Student’s t-test).\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/2cd69a681c8a998aea9d107e.jpg"},{"id":58077235,"identity":"8a8933a7-852f-4ce3-a150-1607c789d59d","added_by":"auto","created_at":"2024-06-10 22:30:45","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":854092,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEffect of miR-193a on tumor growth of Head and Neck cancer (FaDu) cells in nude mice. \u003c/strong\u003eAthymic nude male mice were injected SC with 1X10\u003csup\u003e6\u003c/sup\u003e FaDu cells. When the tumors reached a volume of 200mm\u003csup\u003e3\u003c/sup\u003e, the mice were divided into 2 groups of 8 mice each, with a similar dispersal of tumor volumes. Mice were intraperitoneally injected once a week with either PBS X 1 for the control group, or AD-miR-193a (1x10\u003csup\u003e10\u003c/sup\u003e vp/100g). Tumor volumes (A) and body weights (B) were monitored twice a week, for 3 weeks. Tumor weight (C) was measured after scarifying the animals. The results presented, are the mean ± SD. n=8 mice per experimental group. Statistical significance was determined by a two-tailed student’s t-test (treatment vs. control in each time point) and assigned as **p \u0026lt; 0.01, ***p \u0026lt; 0.001 and by Repeated Measures ANOVA with Tukey HSD post hoc test for the evaluation of changes in tumor volumes over time in each group as well as of differences between control and treatment groups.\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/fb0b3de0d332a8a573d200ee.jpg"},{"id":58076877,"identity":"08e073f6-b066-42a2-9f23-3b5631f18c3c","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":464567,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression levels of miR-193a-3p in HNSCC biopsies\u003c/strong\u003e. Quantitative RT-PCR analysis of the relative expression levels of miR-193a in biopsies of 7 HNSCC cancer tissues and normal adjacent tissue samples from the same patient. Total RNA was extracted from FFP blocks and the expression levels of miRNA-193s were analyzed using Quantitative real-time PCR. (A) Red blots represent miR-193a folds of expression from U6 in normal tissues. Blue blots represent miR-193a folds of expression in patient tissue. (B) Data presentation as means ± SD. Statistical analysis was performed using Student’s \u003cem\u003et\u003c/em\u003e-test with ***P \u0026lt; 0.001 compared to control group.\u003c/p\u003e","description":"","filename":"Figure7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/cce0af478e277b254afa08d9.jpg"},{"id":58076875,"identity":"452af64d-3487-486a-8809-a1aff8d83547","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":788081,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe mechanism of miR-193a in HNSCC cells. \u003c/strong\u003emiR-193a inhibits the mTOR pathway and activate the apoptotic intrinsic pathway through the mitochondrion.\u003c/p\u003e","description":"","filename":"Figure8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/755b45bbcd29035ee536ac29.jpg"},{"id":59173115,"identity":"b7024765-1167-4d16-acf9-882f652ec6d4","added_by":"auto","created_at":"2024-06-27 08:53:35","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5999063,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1_covered_25629370-6a82-472a-a1e9-8ca951840334.pdf"},{"id":58077238,"identity":"943f85ab-5248-45e4-b676-286bb224e6a0","added_by":"auto","created_at":"2024-06-10 22:30:45","extension":"pdf","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":86966,"visible":true,"origin":"","legend":"","description":"","filename":"ERBB4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/4f8f6ed891099d6955148c65.pdf"},{"id":58076878,"identity":"535ad457-ad79-4345-ad93-f1c8cf2d0a40","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"pdf","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":241541,"visible":true,"origin":"","legend":"","description":"","filename":"OriginalGels.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/b0777ef39e81f35fcf63d90b.pdf"},{"id":58076882,"identity":"a9ce8f71-dad4-48dd-9fd3-6af0db3fc809","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"pdf","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":80251,"visible":true,"origin":"","legend":"","description":"","filename":"PIK3R3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/729af4fc6ab47abea506c63b.pdf"},{"id":58077671,"identity":"f1f77c12-9340-4f42-92b9-e2b4c57b34a3","added_by":"auto","created_at":"2024-06-10 22:38:45","extension":"pdf","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":80744,"visible":true,"origin":"","legend":"","description":"","filename":"S6KB2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/ba63e2682e8a600ac467c6ee.pdf"},{"id":58076881,"identity":"7dcdc2f4-7a72-4677-b3a2-deda865183d1","added_by":"auto","created_at":"2024-06-10 22:22:45","extension":"pdf","order_by":14,"title":"","display":"","copyAsset":false,"role":"supplement","size":75133,"visible":true,"origin":"","legend":"","description":"","filename":"mTOR.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4310591/v1/de24b798b5083d815f9d0db7.pdf"}],"financialInterests":"(Not answered)","formattedTitle":"miRNA-193a acts as a tumor suppressor in human head and neck cancer cells and inhibits tumor development in xenograft mice","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4310591/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4310591/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"miRNAs are small non-coding RNA molecules, involved in the regulation of gene expression via binding to messenger RNA (mRNA), thereby preventing protein translation. We found that the promotor region of miR-193a is highly methylated in FaDu head and neck cancer cells, assuming that its expression is suppressed. Moreover, our results indicated that miRNA-193a levels are undetectable in biopsies of head and neck cancer patients. Induction of miR-193a expression by treatment with methyltransferase inhibitor or transduction of head and neck squamous cell carcinoma (HNSCC) cells with miR-193a resulted in a significant decrease in cell viability in a dose and time-dependent manners, as well as induction of apoptosis through the caspase intrinsic pathway. Moreover, miR-193a also inhibited tumour growth in xenograft mice transplanted with FaDu cells. In addition, we found that miR-193a inactivates the AKT/mTOR signaling pathway through the downregulation of PIK3R3, mTOR, S6KB2, and ERBB4. These observations suggest that miR-193a plays an important role in tumor biogenesis and therefore has the potential to serve for diagnostics as well as therapeutics in HNSCC.","manuscriptTitle":"miRNA-193a acts as a tumor suppressor in human head and neck cancer cells and inhibits tumor development in xenograft mice","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-10 22:22:40","doi":"10.21203/rs.3.rs-4310591/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"347b97b3-e417-4496-8aa6-3b476f8668e4","owner":[],"postedDate":"June 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32355511,"name":"Biological sciences/Cancer"},{"id":32355512,"name":"Biological sciences/Cancer/Cancer therapy/Targeted therapies"},{"id":32355513,"name":"Health sciences/Biomarkers/Diagnostic markers"}],"tags":[],"updatedAt":"2024-06-27T08:45:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-10 22:22:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4310591","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4310591","identity":"rs-4310591","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}