Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis
Abstract Background Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear....
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-023-01622-6 |
| _version_ | 1797355643781251072 |
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| author | Shuhui Wu Jingjing Zhu Tingting Jiang Ting Cui Qi Zuo Guibin Zheng Guojun Li Jieyu Zhou Xiang Chen |
| author_facet | Shuhui Wu Jingjing Zhu Tingting Jiang Ting Cui Qi Zuo Guibin Zheng Guojun Li Jieyu Zhou Xiang Chen |
| author_sort | Shuhui Wu |
| collection | DOAJ |
| description | Abstract Background Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. Methods The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. Results ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e−6). Conclusions Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9. Graphical abstract |
| first_indexed | 2024-03-08T14:15:07Z |
| format | Article |
| id | doaj.art-58de1590547347d69eedff02aa05ac79 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-08T14:15:07Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-58de1590547347d69eedff02aa05ac792024-01-14T12:27:29ZengBMCClinical Epigenetics1868-70832024-01-0116111410.1186/s13148-023-01622-6Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axisShuhui Wu0Jingjing Zhu1Tingting Jiang2Ting Cui3Qi Zuo4Guibin Zheng5Guojun Li6Jieyu Zhou7Xiang Chen8Department of Otorhinolaryngology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese MedicineDepartment of Otorhinolaryngology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese MedicineDepartment of Otorhinolaryngology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese MedicineDepartment of Thyroid Surgery, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese MedicineDepartment of Otorhinolaryngology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese MedicineDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Thyroid Surgery, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese MedicineAbstract Background Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. Methods The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. Results ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e−6). Conclusions Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9. Graphical abstracthttps://doi.org/10.1186/s13148-023-01622-6lncRNAACTA2-AS1miR-4428KLF9Papillary thyroid carcinoma |
| spellingShingle | Shuhui Wu Jingjing Zhu Tingting Jiang Ting Cui Qi Zuo Guibin Zheng Guojun Li Jieyu Zhou Xiang Chen Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis Clinical Epigenetics lncRNA ACTA2-AS1 miR-4428 KLF9 Papillary thyroid carcinoma |
| title | Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis |
| title_full | Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis |
| title_fullStr | Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis |
| title_full_unstemmed | Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis |
| title_short | Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis |
| title_sort | long non coding rna acta2 as1 suppresses metastasis of papillary thyroid cancer via regulation of mir 4428 klf9 axis |
| topic | lncRNA ACTA2-AS1 miR-4428 KLF9 Papillary thyroid carcinoma |
| url | https://doi.org/10.1186/s13148-023-01622-6 |
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