ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes
Long non-coding RNAs (lncRNAs) play an essential regulatory role in multiple cancers. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is still unknown. Here, GAS8-AS1, a novel lncRNA that is significantly downregulated in PTC, was selected for further investigation. The roles of GA...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120302936 |
| _version_ | 1818725326728986624 |
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| author | Yuan Qin Wei Sun Zhihong Wang Wenwu Dong Liang He Ting Zhang Liang Shao Hao Zhang |
| author_facet | Yuan Qin Wei Sun Zhihong Wang Wenwu Dong Liang He Ting Zhang Liang Shao Hao Zhang |
| author_sort | Yuan Qin |
| collection | DOAJ |
| description | Long non-coding RNAs (lncRNAs) play an essential regulatory role in multiple cancers. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is still unknown. Here, GAS8-AS1, a novel lncRNA that is significantly downregulated in PTC, was selected for further investigation. The roles of GAS8-AS1 in PTC cells were verified by gain- and loss-of-function experiments. The functional mechanism of GAS8-AS1 on the microRNA (miR)-187-3p/ATG5 axis and miR-1343-3p/ATG7 axis in PTC cells was evaluated using bioinformatics analysis, luciferase reporter assay, Cell Counting Kit-8 (CCK-8) assay, immunohistochemistry analysis, transmission electron microscopy, and immunofluorescence. We found that GAS8-AS1 was downregulated in PTC tissues and cell lines. In patients with PTC, low GAS8-AS1 expression was associated with higher tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM). Functionally, GAS8-AS1 significantly promoted autophagy and inhibited PTC cell proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, GAS8-AS1 acted as a sponge of miR-187-3p and miR-1343-3p and upregulated ATG5 and ATG7 expression, respectively. The transcription factor ATF2 regulated GAS8-AS1 by binding to the GAS8-AS1 promoter. In conclusion, upregulation of ATF2 activated GAS8-AS1–promoted autophagy of PTC cells by sponging oncogenic miR-187-3p and miR-1343-3p and upregulating the expression of ATG5 and ATG7, respectively, making GAS8-AS1 a potential prognostic biomarker and therapeutic target for PTC. |
| first_indexed | 2024-12-17T21:40:32Z |
| format | Article |
| id | doaj.art-6c59484755954029bf4e93b5555636de |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-17T21:40:32Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
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| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-6c59484755954029bf4e93b5555636de2022-12-21T21:31:37ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-12-0122584600ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 AxesYuan Qin0Wei Sun1Zhihong Wang2Wenwu Dong3Liang He4Ting Zhang5Liang Shao6Hao Zhang7Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. ChinaDepartment of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China; Corresponding author: Hao Zhang, Department of Thyroid Surgery, The First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang, Liaoning 110001, P. R. China.Long non-coding RNAs (lncRNAs) play an essential regulatory role in multiple cancers. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is still unknown. Here, GAS8-AS1, a novel lncRNA that is significantly downregulated in PTC, was selected for further investigation. The roles of GAS8-AS1 in PTC cells were verified by gain- and loss-of-function experiments. The functional mechanism of GAS8-AS1 on the microRNA (miR)-187-3p/ATG5 axis and miR-1343-3p/ATG7 axis in PTC cells was evaluated using bioinformatics analysis, luciferase reporter assay, Cell Counting Kit-8 (CCK-8) assay, immunohistochemistry analysis, transmission electron microscopy, and immunofluorescence. We found that GAS8-AS1 was downregulated in PTC tissues and cell lines. In patients with PTC, low GAS8-AS1 expression was associated with higher tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM). Functionally, GAS8-AS1 significantly promoted autophagy and inhibited PTC cell proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, GAS8-AS1 acted as a sponge of miR-187-3p and miR-1343-3p and upregulated ATG5 and ATG7 expression, respectively. The transcription factor ATF2 regulated GAS8-AS1 by binding to the GAS8-AS1 promoter. In conclusion, upregulation of ATF2 activated GAS8-AS1–promoted autophagy of PTC cells by sponging oncogenic miR-187-3p and miR-1343-3p and upregulating the expression of ATG5 and ATG7, respectively, making GAS8-AS1 a potential prognostic biomarker and therapeutic target for PTC.http://www.sciencedirect.com/science/article/pii/S2162253120302936GAS8-AS1lncRNAthyroid cancerautophagytranscription factor |
| spellingShingle | Yuan Qin Wei Sun Zhihong Wang Wenwu Dong Liang He Ting Zhang Liang Shao Hao Zhang ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes Molecular Therapy: Nucleic Acids GAS8-AS1 lncRNA thyroid cancer autophagy transcription factor |
| title | ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes |
| title_full | ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes |
| title_fullStr | ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes |
| title_full_unstemmed | ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes |
| title_short | ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes |
| title_sort | atf2 induced lncrna gas8 as1 promotes autophagy of thyroid cancer cells by targeting the mir 187 3p atg5 and mir 1343 3p atg7 axes |
| topic | GAS8-AS1 lncRNA thyroid cancer autophagy transcription factor |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120302936 |
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