miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation
Abstract Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not be...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04021-y |
| _version_ | 1818454380793298944 |
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| author | Qian Zhang Yun-Fei Yan Qing Lv You-Jie Li Ran-Ran Wang Guang-Bin Sun Li Pan Jin-Xia Hu Ning Xie Can Zhang Bao-Cheng Tian Fei Jiao Sen Xu Ping-Yu Wang Shu-Yang Xie |
| author_facet | Qian Zhang Yun-Fei Yan Qing Lv You-Jie Li Ran-Ran Wang Guang-Bin Sun Li Pan Jin-Xia Hu Ning Xie Can Zhang Bao-Cheng Tian Fei Jiao Sen Xu Ping-Yu Wang Shu-Yang Xie |
| author_sort | Qian Zhang |
| collection | DOAJ |
| description | Abstract Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P. |
| first_indexed | 2024-12-14T21:53:58Z |
| format | Article |
| id | doaj.art-24955051d030494f87af5fa7c33f0c95 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-14T21:53:58Z |
| publishDate | 2021-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-24955051d030494f87af5fa7c33f0c952022-12-21T22:46:09ZengNature Publishing GroupCell Death and Disease2041-48892021-07-0112811310.1038/s41419-021-04021-ymiR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferationQian Zhang0Yun-Fei Yan1Qing Lv2You-Jie Li3Ran-Ran Wang4Guang-Bin Sun5Li Pan6Jin-Xia Hu7Ning Xie8Can Zhang9Bao-Cheng Tian10Fei Jiao11Sen Xu12Ping-Yu Wang13Shu-Yang Xie14Department of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Chest Surgery, YanTaiShan HospitalGenetics and Aging Research Unit, Mass General Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital and Harvard Medical SchoolDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityDepartment of Biochemistry and Molecular Biology, Binzhou Medical UniversityAbstract Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.https://doi.org/10.1038/s41419-021-04021-y |
| spellingShingle | Qian Zhang Yun-Fei Yan Qing Lv You-Jie Li Ran-Ran Wang Guang-Bin Sun Li Pan Jin-Xia Hu Ning Xie Can Zhang Bao-Cheng Tian Fei Jiao Sen Xu Ping-Yu Wang Shu-Yang Xie miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation Cell Death and Disease |
| title | miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation |
| title_full | miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation |
| title_fullStr | miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation |
| title_full_unstemmed | miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation |
| title_short | miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation |
| title_sort | mir 4293 upregulates lncrna wfdc21p by suppressing mrna decapping enzyme 2 to promote lung carcinoma proliferation |
| url | https://doi.org/10.1038/s41419-021-04021-y |
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