A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells
Abstract Objective While long non-coding RNAs (lncRNAs) are increasingly recognized as sources of functional micropeptides, their roles in non-small cell lung cancer (NSCLC) remain poorly characterized. This study investigates the therapeutic potential and molecular mechanism of LINC00472-encoded po...
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BMC
2025-07-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03901-z |
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| author | Lei Xu Haoyong Kuang Haodong Peng Sen Wu Yu Bai Xiangbo Jia Wenjian Yao |
| author_facet | Lei Xu Haoyong Kuang Haodong Peng Sen Wu Yu Bai Xiangbo Jia Wenjian Yao |
| author_sort | Lei Xu |
| collection | DOAJ |
| description | Abstract Objective While long non-coding RNAs (lncRNAs) are increasingly recognized as sources of functional micropeptides, their roles in non-small cell lung cancer (NSCLC) remain poorly characterized. This study investigates the therapeutic potential and molecular mechanism of LINC00472-encoded polypeptide in NSCLC. Methods Through integration of ribosome profiling, transcriptomics, and co-expression analysis, we systematically identified lncRNA-encoded polypeptides in NSCLC. Translational competence was validated via ribosome affinity purification (TRAP), Western blot, and immunofluorescence (IF). Functional assays (CCK-8, EdU, wound healing, transwell) and xenograft models assessed anti-tumor effects. HDAC2/SP1 interaction dynamics were analyzed by co-IP and luciferase reporter systems. Results Multi-omics screening identified LINC00472 as a bifunctional transcript encoding a 15-aa polypeptide (LINC00472-ORF). LINC00472-ORF exhibited potent tumor-suppressive activity, reducing NSCLC proliferation and motility in vitro, while suppressing xenograft growth in vivo. Mechanistically, LINC00472-ORF disrupted HDAC2/SP1 interaction, inducing SP1 hyperacetylation, cytoplasmic retention, and transcriptional inactivation of downstream oncogenic genes. Conclusion We unveil LINC00472-ORF as a dual-function therapeutic agent that targets the HDAC2/SP1 axis to inhibit NSCLC progression. Graphical Abstract |
| format | Article |
| id | doaj-art-1dff690baca947e7b0f144c6a6edea52 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-1dff690baca947e7b0f144c6a6edea522025-08-20T04:02:45ZengBMCCancer Cell International1475-28672025-07-0125111510.1186/s12935-025-03901-zA LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cellsLei Xu0Haoyong Kuang1Haodong Peng2Sen Wu3Yu Bai4Xiangbo Jia5Wenjian Yao6Department of Thoracic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan UniversityDepartment of Thoracic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Thoracic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s HospitalDepartment of Thoracic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan UniversityDepartment of Pathology, Xinxiang Medical UniversityDepartment of Thoracic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan UniversityDepartment of Thoracic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan UniversityAbstract Objective While long non-coding RNAs (lncRNAs) are increasingly recognized as sources of functional micropeptides, their roles in non-small cell lung cancer (NSCLC) remain poorly characterized. This study investigates the therapeutic potential and molecular mechanism of LINC00472-encoded polypeptide in NSCLC. Methods Through integration of ribosome profiling, transcriptomics, and co-expression analysis, we systematically identified lncRNA-encoded polypeptides in NSCLC. Translational competence was validated via ribosome affinity purification (TRAP), Western blot, and immunofluorescence (IF). Functional assays (CCK-8, EdU, wound healing, transwell) and xenograft models assessed anti-tumor effects. HDAC2/SP1 interaction dynamics were analyzed by co-IP and luciferase reporter systems. Results Multi-omics screening identified LINC00472 as a bifunctional transcript encoding a 15-aa polypeptide (LINC00472-ORF). LINC00472-ORF exhibited potent tumor-suppressive activity, reducing NSCLC proliferation and motility in vitro, while suppressing xenograft growth in vivo. Mechanistically, LINC00472-ORF disrupted HDAC2/SP1 interaction, inducing SP1 hyperacetylation, cytoplasmic retention, and transcriptional inactivation of downstream oncogenic genes. Conclusion We unveil LINC00472-ORF as a dual-function therapeutic agent that targets the HDAC2/SP1 axis to inhibit NSCLC progression. Graphical Abstracthttps://doi.org/10.1186/s12935-025-03901-zlncRNA-encoded polypeptideLINC00472HDAC2/SP1 axisMulti-omics screeningNSCLCEpigenetic-transcriptional regulation |
| spellingShingle | Lei Xu Haoyong Kuang Haodong Peng Sen Wu Yu Bai Xiangbo Jia Wenjian Yao A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells Cancer Cell International lncRNA-encoded polypeptide LINC00472 HDAC2/SP1 axis Multi-omics screening NSCLC Epigenetic-transcriptional regulation |
| title | A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells |
| title_full | A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells |
| title_fullStr | A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells |
| title_full_unstemmed | A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells |
| title_short | A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells |
| title_sort | linc00472 encoded polypeptide impedes migration and proliferation through modulation of the hdac2 sp1 axis in non small cell lung cancer cells |
| topic | lncRNA-encoded polypeptide LINC00472 HDAC2/SP1 axis Multi-omics screening NSCLC Epigenetic-transcriptional regulation |
| url | https://doi.org/10.1186/s12935-025-03901-z |
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