The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells
Abstract Background Ovarian cancer is the fifth leading cause of cancer deaths in women worldwide. LncRNACCAT1 was reported to play a critical role in cell metastasis of ovarian cancer. However, little is known about the detailed mechanism of how CCAT1 enhances TGFβ1-induced EMT of ovarian cancer ce...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-018-0604-1 |
| _version_ | 1818545945992757248 |
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| author | Yang Mu Na Li Yu-Lan Cui |
| author_facet | Yang Mu Na Li Yu-Lan Cui |
| author_sort | Yang Mu |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer is the fifth leading cause of cancer deaths in women worldwide. LncRNACCAT1 was reported to play a critical role in cell metastasis of ovarian cancer. However, little is known about the detailed mechanism of how CCAT1 enhances TGFβ1-induced EMT of ovarian cancer cells. Methods We used RT-qPCR to examine the level of miR-490-3p and CCAT1 and western blot to detect the protein level of TGFβR1 and EMT-associated markers. We utilized luciferase reporter assay to confirm the direct interaction of CCAT1 or TGFβ1 with miR-490-3p. Wound healing and invasion assay were employed to investigate the role of CCAT1 and miR-490-3p in the TGFβ1-induced migration and cell invasion of ovarian cancer cells, respectively. Results TGFβ1 stimulated the expression of CCAT1. And CCAT1 knockdown decreased cell migration, invasion and EMT-associated markers expression of ovarian cancer cells treated with TGFβ1. CCAT1 directly targeted and downregulated miR-490-3p, then increasing TGFβR1 level. miR-490-3p was shown to regulate cell invasion, migration and EMT markers expression via TGFβR1. In addition, we also observed that miR-490-3p was essential for TGFβ1-induced tumor cell invasion and migration influenced by CCAT1. CCAT1 level was significantly higher in tumors than adjacent normal tissue, in contrast, miR-490-3p level was lower in ovarian tumors. Conclusion Here, we reveal that CCAT1 contributes to TGFβ1-induced EMT of ovarian tumor cells through miR-490-3p/TGFR1 axis. These findings will provide deep insights into the mechanism by which CCAT1 exerts its oncogenic role in ovarian cancer progression and facilitate developing novel therapeutical therapies for treating ovarian cancer. |
| first_indexed | 2024-12-12T07:46:36Z |
| format | Article |
| id | doaj.art-3a3ac385267446b3a7304d8bde9c311d |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-12T07:46:36Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-3a3ac385267446b3a7304d8bde9c311d2022-12-22T00:32:35ZengBMCCancer Cell International1475-28672018-09-0118111210.1186/s12935-018-0604-1The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cellsYang Mu0Na Li1Yu-Lan Cui2Department of Gynaecology, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Gynaecology, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Gynaecology, The Second Affiliated Hospital of Harbin Medical UniversityAbstract Background Ovarian cancer is the fifth leading cause of cancer deaths in women worldwide. LncRNACCAT1 was reported to play a critical role in cell metastasis of ovarian cancer. However, little is known about the detailed mechanism of how CCAT1 enhances TGFβ1-induced EMT of ovarian cancer cells. Methods We used RT-qPCR to examine the level of miR-490-3p and CCAT1 and western blot to detect the protein level of TGFβR1 and EMT-associated markers. We utilized luciferase reporter assay to confirm the direct interaction of CCAT1 or TGFβ1 with miR-490-3p. Wound healing and invasion assay were employed to investigate the role of CCAT1 and miR-490-3p in the TGFβ1-induced migration and cell invasion of ovarian cancer cells, respectively. Results TGFβ1 stimulated the expression of CCAT1. And CCAT1 knockdown decreased cell migration, invasion and EMT-associated markers expression of ovarian cancer cells treated with TGFβ1. CCAT1 directly targeted and downregulated miR-490-3p, then increasing TGFβR1 level. miR-490-3p was shown to regulate cell invasion, migration and EMT markers expression via TGFβR1. In addition, we also observed that miR-490-3p was essential for TGFβ1-induced tumor cell invasion and migration influenced by CCAT1. CCAT1 level was significantly higher in tumors than adjacent normal tissue, in contrast, miR-490-3p level was lower in ovarian tumors. Conclusion Here, we reveal that CCAT1 contributes to TGFβ1-induced EMT of ovarian tumor cells through miR-490-3p/TGFR1 axis. These findings will provide deep insights into the mechanism by which CCAT1 exerts its oncogenic role in ovarian cancer progression and facilitate developing novel therapeutical therapies for treating ovarian cancer.http://link.springer.com/article/10.1186/s12935-018-0604-1Ovarian cancerEMTCCAT1miR-490-3pTGFβ1/TGFβR1 |
| spellingShingle | Yang Mu Na Li Yu-Lan Cui The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells Cancer Cell International Ovarian cancer EMT CCAT1 miR-490-3p TGFβ1/TGFβR1 |
| title | The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells |
| title_full | The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells |
| title_fullStr | The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells |
| title_full_unstemmed | The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells |
| title_short | The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells |
| title_sort | lncrna ccat1 upregulates tgfβr1 via sponging mir 490 3p to promote tgfβ1 induced emt of ovarian cancer cells |
| topic | Ovarian cancer EMT CCAT1 miR-490-3p TGFβ1/TGFβR1 |
| url | http://link.springer.com/article/10.1186/s12935-018-0604-1 |
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