FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway
Abstract Background Lung adenocarcinoma (LUAD) is highly malignant and associated with poor prognoses in patients worldwide. There has been widespread recognition that lncRNAs are tightly linked to LUAD tumorigenesis and development. Here, we identified that the LINC00621 level was increased in LUAD...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.14986 |
| _version_ | 1797773551107833856 |
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| author | Jingjing Wei Haiyang Yu Tan Liu Ziming Wang Chuandong Lang Yueyin Pan |
| author_facet | Jingjing Wei Haiyang Yu Tan Liu Ziming Wang Chuandong Lang Yueyin Pan |
| author_sort | Jingjing Wei |
| collection | DOAJ |
| description | Abstract Background Lung adenocarcinoma (LUAD) is highly malignant and associated with poor prognoses in patients worldwide. There has been widespread recognition that lncRNAs are tightly linked to LUAD tumorigenesis and development. Here, we identified that the LINC00621 level was increased in LUAD tissues and concerned with the poor prognoses in LUAD patients. Methods Bioinformatical analysis and RT‐qPCR determined the level of LINC00621 in LUAD tissues and cell lines. The admeasurement of the proliferation, migration, and invasion abilities of LUAD cells was utilized in the CCK8 and Transwell formulas. Luciferase reporter assay was used to corroborate the downstream target genes of LINC00621. The phosphorylated SMAD3 protein was tested by Western blotting assay. The impression of LINC00621 knockdown on LUAD tumor growth and metastasis put into effect by murine models. ChIP‐qPCR assay was carried out to verify the transcriptional regulation by FOXA1 on LINC00621. Results In vitro, the knockdown of LINC00621 significantly reduced the proliferative, migrating, and invasive abilities, the same was true for tumorigenesis and metastasis in vivo. MiR‐34a‐5p as a straight target of LINC00621 was ascertained, and LUAD patients with inferior miR‐34a‐5p levels had undesirable prognoses. Furthermore, TGFBR1 is an immediate and functional connection site of miR‐34a‐5p. Collectively, LINC00621 can sponge miR‐34a‐5p and upregulate TGFBR1 levels, which further sensitized TGF‐β signaling pathway. Finally, it was revealed that FOXA1 transcriptionally upregulated LINC00621. Conclusion This study uncovered that FOXA1‐induced LINC00621 promotes LUAD progression via the miR‐34a‐5p/TGFBR1/TGF‐β axis, and is one novel therapeutic target that may be used in LUAD treatment. |
| first_indexed | 2024-03-12T22:08:06Z |
| format | Article |
| id | doaj.art-7884129ee02d42c38f88d724a36fa9f7 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-03-12T22:08:06Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-7884129ee02d42c38f88d724a36fa9f72023-07-24T08:06:25ZengWileyThoracic Cancer1759-77061759-77142023-07-0114212026203710.1111/1759-7714.14986FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathwayJingjing Wei0Haiyang Yu1Tan Liu2Ziming Wang3Chuandong Lang4Yueyin Pan5Department of Tumor Chemotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Tumor Chemotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Medical Oncology 901 Hospital of Joint Logistics Support Force of People Liberation Army Hefei ChinaDepartment of Tumor Chemotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Tumor Chemotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaAbstract Background Lung adenocarcinoma (LUAD) is highly malignant and associated with poor prognoses in patients worldwide. There has been widespread recognition that lncRNAs are tightly linked to LUAD tumorigenesis and development. Here, we identified that the LINC00621 level was increased in LUAD tissues and concerned with the poor prognoses in LUAD patients. Methods Bioinformatical analysis and RT‐qPCR determined the level of LINC00621 in LUAD tissues and cell lines. The admeasurement of the proliferation, migration, and invasion abilities of LUAD cells was utilized in the CCK8 and Transwell formulas. Luciferase reporter assay was used to corroborate the downstream target genes of LINC00621. The phosphorylated SMAD3 protein was tested by Western blotting assay. The impression of LINC00621 knockdown on LUAD tumor growth and metastasis put into effect by murine models. ChIP‐qPCR assay was carried out to verify the transcriptional regulation by FOXA1 on LINC00621. Results In vitro, the knockdown of LINC00621 significantly reduced the proliferative, migrating, and invasive abilities, the same was true for tumorigenesis and metastasis in vivo. MiR‐34a‐5p as a straight target of LINC00621 was ascertained, and LUAD patients with inferior miR‐34a‐5p levels had undesirable prognoses. Furthermore, TGFBR1 is an immediate and functional connection site of miR‐34a‐5p. Collectively, LINC00621 can sponge miR‐34a‐5p and upregulate TGFBR1 levels, which further sensitized TGF‐β signaling pathway. Finally, it was revealed that FOXA1 transcriptionally upregulated LINC00621. Conclusion This study uncovered that FOXA1‐induced LINC00621 promotes LUAD progression via the miR‐34a‐5p/TGFBR1/TGF‐β axis, and is one novel therapeutic target that may be used in LUAD treatment.https://doi.org/10.1111/1759-7714.14986FOXA1LINC00621lung adenocarcinomaMiR‐34a‐5pTGF‐β |
| spellingShingle | Jingjing Wei Haiyang Yu Tan Liu Ziming Wang Chuandong Lang Yueyin Pan FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway Thoracic Cancer FOXA1 LINC00621 lung adenocarcinoma MiR‐34a‐5p TGF‐β |
| title | FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway |
| title_full | FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway |
| title_fullStr | FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway |
| title_full_unstemmed | FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway |
| title_short | FOXA1‐induced LINC00621 promotes lung adenocarcinoma progression via activating the TGF‐β signaling pathway |
| title_sort | foxa1 induced linc00621 promotes lung adenocarcinoma progression via activating the tgf β signaling pathway |
| topic | FOXA1 LINC00621 lung adenocarcinoma MiR‐34a‐5p TGF‐β |
| url | https://doi.org/10.1111/1759-7714.14986 |
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