{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T07:25:39Z","timestamp":1787210739808,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hereditas"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Lung adenocarcinoma (LUAD) poses significant clinical challenges due to its heterogeneity and metastatic potential, necessitating deeper molecular characterization. This study investigated the role of miR-6791-5p and its target\n                      <jats:italic>RASL12<\/jats:italic>\n                      in LUAD progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Expression profiles and prognostic relevance were analyzed in 203 LUAD patients, cell lines, and public databases. Biological functions were evaluated through CCK-8, Transwell, independent\n                      <jats:italic>RASL12<\/jats:italic>\n                      knockdown, and rescue assays. Interactions were validated by dual-luciferase assays. Downstream pathways were explored via Gene Set Enrichment Analysis (GSEA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      miR-6791-5p was significantly upregulated in LUAD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), independently predicting poor overall survival (HR\u2009=\u20092.411,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Functionally, miR-6791-5p promoted LUAD cell proliferation, migration, and invasion.\n                      <jats:italic>RASL12<\/jats:italic>\n                      was confirmed as a direct target, exhibiting decreased mRNA and protein expression in tumors that negatively correlated with miR-6791-5p. Independent\n                      <jats:italic>RASL12<\/jats:italic>\n                      knockdown enhanced tumor aggressiveness, while its co-knockdown partially reversed the tumor-suppressive effects of miR-6791-5p inhibition. GSEA linked this axis to cell adhesion signaling dynamics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      miR-6791-5p acts as an oncogene in LUAD by directly targeting the tumor suppressor\n                      <jats:italic>RASL12<\/jats:italic>\n                      . This axis modulates malignant phenotypes, representing a promising prognostic biomarker and potential therapeutic candidate.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41065-026-00697-4","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:13:06Z","timestamp":1784949186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting RASL12 by miR-6791-5p fuels malignant progression in lung adenocarcinoma"],"prefix":"10.1186","volume":"163","author":[{"given":"Lu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"issue":"3","key":"697_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"Cancer J Clin"},{"key":"697_CR2","doi-asserted-by":"publisher","first-page":"581919","DOI":"10.3389\/fcell.2020.581919","volume":"8","author":"Q Guo","year":"2020","unstructured":"Guo Q, Ke X-X, Fang S-X, Gao W-L, Song Y-X, Chen C, et al. PAQR3 inhibits non-small cell lung cancer growth by regulating the NF-\u03baB\/p53\/Bax axis. Front Cell Dev Biology. 2020;8:581919.","journal-title":"Front Cell Dev Biology"},{"key":"697_CR3","doi-asserted-by":"publisher","first-page":"100915","DOI":"10.1016\/j.drup.2022.100915","volume":"67","author":"Z Yu","year":"2023","unstructured":"Yu Z, Tang H, Chen S, Xie Y, Shi L, Xia S, et al. Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updates. 2023;67:100915.","journal-title":"Drug Resist Updates"},{"issue":"1","key":"697_CR4","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13046-024-03026-7","volume":"43","author":"F Ren","year":"2024","unstructured":"Ren F, Fei Q, Qiu K, Zhang Y, Zhang H, Sun L. Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation. J Experimental Clin Cancer Res. 2024;43(1):96.","journal-title":"J Experimental Clin Cancer Res"},{"issue":"1","key":"697_CR5","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41392-025-02148-4","volume":"10","author":"Y Li","year":"2025","unstructured":"Li Y, Liu F, Cai Q, Deng L, Ouyang Q, Zhang XH-F, et al. Invasion and metastasis in cancer: molecular insights and therapeutic targets. Signal Transduct Target therapy. 2025;10(1):57.","journal-title":"Signal Transduct Target therapy"},{"issue":"15","key":"697_CR6","doi-asserted-by":"publisher","first-page":"3725","DOI":"10.1039\/D4BM00488D","volume":"12","author":"Y Deng","year":"2024","unstructured":"Deng Y, Guo M, Zhou L, Huang Y, Srivastava S, Kumar A, et al. Prospects, advances and biological applications of MOF-based platform for the treatment of lung cancer. Biomaterials Sci. 2024;12(15):3725\u201344.","journal-title":"Biomaterials Sci"},{"issue":"3","key":"697_CR7","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1002\/bit.28029","volume":"119","author":"V Rani","year":"2022","unstructured":"Rani V, Sengar RS. Biogenesis and mechanisms of microRNA-mediated gene regulation. Biotechnol Bioeng. 2022;119(3):685\u201392.","journal-title":"Biotechnol Bioeng"},{"issue":"4","key":"697_CR8","doi-asserted-by":"publisher","first-page":"e1701","DOI":"10.1002\/wrna.1701","volume":"13","author":"PM Fr\u00e9d\u00e9rick","year":"2022","unstructured":"Fr\u00e9d\u00e9rick PM, Simard MJ. Regulation and different functions of the animal microRNA-induced silencing complex. Wiley Interdisciplinary Reviews: RNA. 2022;13(4):e1701.","journal-title":"Wiley Interdisciplinary Reviews: RNA"},{"issue":"1","key":"697_CR9","doi-asserted-by":"publisher","first-page":"52","DOI":"10.18097\/pbmc20247001052","volume":"70","author":"T Kalinina","year":"2024","unstructured":"Kalinina T, Kononchuk V, Valembakhov I, Pustylnyak V, Kozlov V, Gulyaeva L. Expression of AhR-regulated miRNAs in non-small cell lung cancer in smokers and never smokers. Biomeditsinskaya Khim. 2024;70(1):52\u201360.","journal-title":"Biomeditsinskaya Khim"},{"issue":"8","key":"697_CR10","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.7150\/jca.93343","volume":"15","author":"M He","year":"2024","unstructured":"He M, Zhang H, Zhang Y, Ding Y, Zhang F, Kang Y. Systematic analysis to identify the MIR99AHG-has-miR-21-5p-EHD1 CeRNA regulatory network as potential biomarkers in lung cancer. J Cancer. 2024;15(8):2391.","journal-title":"J Cancer"},{"key":"697_CR11","doi-asserted-by":"publisher","first-page":"116539","DOI":"10.1016\/j.lfs.2019.06.014","volume":"231","author":"J Zhong","year":"2019","unstructured":"Zhong J, Ren X, Chen Z, Zhang H, Zhou L, Yuan J, et al. miR-21-5p promotes lung adenocarcinoma progression partially through targeting SET\/TAF-I\u03b1. Life Sci. 2019;231:116539.","journal-title":"Life Sci"},{"key":"697_CR12","doi-asserted-by":"publisher","first-page":"1561081","DOI":"10.3389\/fimmu.2025.1561081","volume":"16","author":"X Zhang","year":"2025","unstructured":"Zhang X, Huang X, Zhang X, Lai L, Zhu B, Lin P, et al. The miR-941\/FOXN4\/TGF-\u03b2 feedback loop induces N2 polarization of neutrophils and enhances tumor progression of lung adenocarcinoma. Front Immunol. 2025;16:1561081.","journal-title":"Front Immunol"},{"issue":"9","key":"697_CR13","doi-asserted-by":"publisher","first-page":"2746","DOI":"10.7150\/jca.89733","volume":"15","author":"X Bi","year":"2024","unstructured":"Bi X, Wang L, Li H, Ma Y, Guo R, Yue J, et al. MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting SHMT2. J Cancer. 2024;15(9):2746.","journal-title":"J Cancer"},{"issue":"1","key":"697_CR14","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12938-021-00952-x","volume":"20","author":"Y Li","year":"2021","unstructured":"Li Y, Yu X, Zhang Y, Wang X, Zhao L, Liu D, et al. Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis. Biomed Eng Online. 2021;20(1):117.","journal-title":"Biomed Eng Online"},{"issue":"5","key":"697_CR15","first-page":"551","volume":"14","author":"Z Liu","year":"2021","unstructured":"Liu Z, Liu X, Cai R, Liu M, Wang R. Identification of a tumor microenvironment-associated prognostic gene signature in bladder cancer by integrated bioinformatic analysis. Int J Clin Exp Pathol. 2021;14(5):551.","journal-title":"Int J Clin Exp Pathol"},{"key":"697_CR16","doi-asserted-by":"publisher","first-page":"1690174","DOI":"10.3389\/fimmu.2025.1690174","volume":"16","author":"W Qian","year":"2025","unstructured":"Qian W, Wu K, Shen Z, Ni B, Zheng H, Liu Y, et al. Identification of CAF signature genes and construction of CAF-based risk signature in hepatocellular carcinoma by multi-omics analysis. Front Immunol. 2025;16:1690174.","journal-title":"Front Immunol"},{"issue":"7","key":"697_CR17","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.3390\/cancers14071759","volume":"14","author":"L Seguin","year":"2022","unstructured":"Seguin L, Durandy M, Feral CC. Lung adenocarcinoma tumor origin: a guide for personalized medicine. Cancers. 2022;14(7):1759.","journal-title":"Cancers"},{"issue":"6","key":"697_CR18","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1158\/2159-8290.CD-20-1274","volume":"11","author":"D Tavernari","year":"2021","unstructured":"Tavernari D, Battistello E, Dheilly E, Petruzzella AS, Mina M, Sordet-Dessimoz J, et al. Nongenetic evolution drives lung adenocarcinoma spatial heterogeneity and progression. Cancer Discov. 2021;11(6):1490\u2013507.","journal-title":"Cancer Discov"},{"key":"697_CR19","doi-asserted-by":"crossref","unstructured":"Mittal V. Epithelial mesenchymal transition in aggressive lung cancers. Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. 2015;8(18):37\u201356.","DOI":"10.1007\/978-3-319-24932-2_3"},{"key":"697_CR20","doi-asserted-by":"crossref","unstructured":"Xu Q, Ye L, Huang L, Zhou L, Chen X, Ye M et al. Serum exosomal miRNA might be a novel liquid biopsy to identify leptomeningeal metastasis in non-small cell lung cancer. OncoTargets therapy. 2021;14:2327\u201335.","DOI":"10.2147\/OTT.S291611"},{"issue":"1","key":"697_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12943-022-01505-z","volume":"21","author":"W Li","year":"2022","unstructured":"Li W, Liu J-B, Hou L-K, Yu F, Zhang J, Wu W, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer. 2022;21(1):25.","journal-title":"Mol Cancer"},{"key":"697_CR22","doi-asserted-by":"publisher","first-page":"630718","DOI":"10.3389\/fmolb.2021.630718","volume":"8","author":"X He","year":"2021","unstructured":"He X, Park S, Chen Y, Lee H. Extracellular vesicle-associated miRNAs as a biomarker for lung cancer in liquid biopsy. Front Mol Biosci. 2021;8:630718.","journal-title":"Front Mol Biosci"},{"key":"697_CR23","doi-asserted-by":"publisher","unstructured":"Liu H, Karsidag I, Golin R, Wu G. Bridging Discovery and Treatment: Cancer Biomarker. Cancers (Basel). 2025;17(22). https:\/\/doi.org\/10.3390\/cancers17223720.","DOI":"10.3390\/cancers17223720"},{"issue":"10","key":"697_CR24","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.3390\/jcm10102110","volume":"10","author":"O Cho","year":"2021","unstructured":"Cho O, Kim D-W, Cheong J-Y. Plasma exosomal miRNA levels after radiotherapy are associated with early progression and metastasis of cervical cancer: a pilot study. J Clin Med. 2021;10(10):2110.","journal-title":"J Clin Med"},{"issue":"1","key":"697_CR25","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12943-022-01539-3","volume":"21","author":"S-T Xue","year":"2022","unstructured":"Xue S-T, Zheng B, Cao S-Q, Ding J-C, Hu G-S, Liu W, et al. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p\/PAK6 axis. Mol Cancer. 2022;21(1):69.","journal-title":"Mol Cancer"},{"issue":"1","key":"697_CR26","doi-asserted-by":"publisher","first-page":"7530853","DOI":"10.1155\/2016\/7530853","volume":"2016","author":"Y Luo","year":"2016","unstructured":"Luo Y, Wen X, Wang L, Gao J, Wang Z, Zhang C, et al. Identification of MicroRNAs Involved in Growth Arrest and Apoptosis in Hydrogen Peroxide-Treated Human Hepatocellular Carcinoma Cell Line HepG2. Oxidative Med Cell Longev. 2016;2016(1):7530853.","journal-title":"Oxidative Med Cell Longev"},{"issue":"4","key":"697_CR27","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1093\/nar\/gkad1142","volume":"52","author":"C Diener","year":"2024","unstructured":"Diener C, Keller A, Meese E. The miRNA\u2013target interactions: an underestimated intricacy. Nucleic Acids Res. 2024;52(4):1544\u201357.","journal-title":"Nucleic Acids Res"},{"key":"697_CR28","unstructured":"Seetharaman Thillai Villalan D. RAS small GTPase signalling to the enigmatic RASSF death effectors. 2020."},{"issue":"1","key":"697_CR29","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12935-025-03788-w","volume":"25","author":"X Zhong","year":"2025","unstructured":"Zhong X, Yang Y, He H, Xiong Y, Zhong M, Wang S, et al. Integrating multi-cohort machine learning and clinical sample validation to explore peripheral blood mRNA diagnostic biomarkers for prostate cancer. Cancer Cell Int. 2025;25(1):158.","journal-title":"Cancer Cell Int"},{"key":"697_CR30","doi-asserted-by":"publisher","first-page":"e16447","DOI":"10.7717\/peerj.16447","volume":"11","author":"Q Tian","year":"2023","unstructured":"Tian Q, Liu X, Li A, Wu H, Xie Y, Zhang H, et al. LINC01936 inhibits the proliferation and metastasis of lung squamous cell carcinoma probably by EMT signaling and immune infiltration. PeerJ. 2023;11:e16447.","journal-title":"PeerJ"},{"issue":"21","key":"697_CR31","doi-asserted-by":"publisher","first-page":"e71317","DOI":"10.1002\/cam4.71317","volume":"14","author":"Y Chen","year":"2025","unstructured":"Chen Y, Bai M, Liu M, Zhang Z, Jiang C, Li K, et al. Metabolic Reprogramming in Lung Cancer: Hallmarks, Mechanisms, and Targeted Strategies to Overcome Immune Resistance. Cancer Med. 2025;14(21):e71317. https:\/\/doi.org\/10.1002\/cam4.71317.","journal-title":"Cancer Med"},{"issue":"1","key":"697_CR32","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s12672-026-04464-9","volume":"17","author":"Z Diao","year":"2026","unstructured":"Diao Z, Chen Y, Guo W. Pan-cancer multi-dimensional characterization and biological significance of cholesterol 25-hydroxylase (CH25H). Discover Oncol. 2026;17(1):315. https:\/\/doi.org\/10.1007\/s12672-026-04464-9.","journal-title":"Discover Oncol"},{"key":"697_CR33","doi-asserted-by":"publisher","unstructured":"Chen Y, Lin R, Pan J, Lau LY, Hua Y, Chen Q, et al. TMEM132A is associated with metabolic reprogramming, macrophage-oriented immune remodeling, and breast cancer progression. Clin experimental Med. 2026;26(1). https:\/\/doi.org\/10.1007\/s10238-026-02125-3.","DOI":"10.1007\/s10238-026-02125-3"},{"issue":"1","key":"697_CR34","doi-asserted-by":"publisher","first-page":"19055","DOI":"10.1038\/s41598-023-45774-0","volume":"13","author":"H Liu","year":"2023","unstructured":"Liu H, Tang T. MAPK signaling pathway-based glioma subtypes, machine-learning risk model, and key hub proteins identification. Sci Rep. 2023;13(1):19055. https:\/\/doi.org\/10.1038\/s41598-023-45774-0.","journal-title":"Sci Rep"},{"key":"697_CR35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.cancergen.2025.06.008","volume":"296\u2013297","author":"Y Liu","year":"2025","unstructured":"Liu Y, He Q, Zhu L, Zhong M, Zhuang H, Zhao N, et al. TRIM29 promotes glioblastoma progression via ubiquitinating NEFL and activating the PI3K\/AKT signaling pathway. Cancer Genet. 2025;296\u2013297:88\u201399. https:\/\/doi.org\/10.1016\/j.cancergen.2025.06.008.","journal-title":"Cancer Genet"}],"container-title":["Hereditas"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41065-026-00697-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41065-026-00697-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41065-026-00697-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T07:10:40Z","timestamp":1787209840000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41065-026-00697-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["697"],"URL":"https:\/\/doi.org\/10.1186\/s41065-026-00697-4","relation":{},"ISSN":["1601-5223"],"issn-type":[{"value":"1601-5223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]},"assertion":[{"value":"23 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of THE FOURTH HOSPITAL OF TONGXIANG before the study began. The written informed consent has been obtained from the participants involved.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"89"}}