Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling
Long noncoding RNA (lncRNA) MEG3 has been widely reported to be decreased in a growing list of primary human tumours and play a key role in tumour suppression. However, there are few reports about MEG3 expression and function in oesophagal squamous cell carcinoma (ESCC). Here, we found that MEG3 exp...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-12-01
|
| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2019.1602538 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849317031639252992 |
|---|---|
| author | Ji Ma Teng-Fei Li Xin-Wei Han Hui-Feng Yuan |
| author_facet | Ji Ma Teng-Fei Li Xin-Wei Han Hui-Feng Yuan |
| author_sort | Ji Ma |
| collection | DOAJ |
| description | Long noncoding RNA (lncRNA) MEG3 has been widely reported to be decreased in a growing list of primary human tumours and play a key role in tumour suppression. However, there are few reports about MEG3 expression and function in oesophagal squamous cell carcinoma (ESCC). Here, we found that MEG3 expression was significantly downregulated in tumour tissues, and its low expression was associated with large tumour size, lymph node metastasis and advanced clinical stage in ESCC patients. Univariate and multivariate analyses revealed low expression of MEG3 as an independent predictor for disease-free survival and overall survival. Cell experiments showed that MEG3 inhibited ESCC cell proliferation, migration and invasion. Subsequently, miR-4261 was identified and confirmed to be the target of MEG3, and MEG3 functions, at least in part, by targeting miR-4261. Additionally, Dickkopf-2 (DKK2), a Wnt/β-catenin signalling inhibitor, was identified to be a target of miR-4261. MEG3 interacted with miR-4261, derepressed DKK2 and blocked the Wnt/β-catenin signalling, thereby inhibiting tumourigenesis and progression in ESCC. In vivo experiments also confirmed this conclusion. Our study for the first time elaborated the critical role of MEG3-miR-4261-DKK2-Wnt/β-catenin signalling axis in ESCC, and MEG3 could represent a novel diagnostic and prognostic biomarker and therapeutic target in ESCC. |
| format | Article |
| id | doaj-art-e2172b7d03284f7d94407c13ea34ffb1 |
| institution | Kabale University |
| issn | 2169-1401 2169-141X |
| language | English |
| publishDate | 2019-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj-art-e2172b7d03284f7d94407c13ea34ffb12025-08-20T03:51:24ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2019-12-014711513152310.1080/21691401.2019.1602538Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signallingJi Ma0Teng-Fei Li1Xin-Wei Han2Hui-Feng Yuan3Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaLong noncoding RNA (lncRNA) MEG3 has been widely reported to be decreased in a growing list of primary human tumours and play a key role in tumour suppression. However, there are few reports about MEG3 expression and function in oesophagal squamous cell carcinoma (ESCC). Here, we found that MEG3 expression was significantly downregulated in tumour tissues, and its low expression was associated with large tumour size, lymph node metastasis and advanced clinical stage in ESCC patients. Univariate and multivariate analyses revealed low expression of MEG3 as an independent predictor for disease-free survival and overall survival. Cell experiments showed that MEG3 inhibited ESCC cell proliferation, migration and invasion. Subsequently, miR-4261 was identified and confirmed to be the target of MEG3, and MEG3 functions, at least in part, by targeting miR-4261. Additionally, Dickkopf-2 (DKK2), a Wnt/β-catenin signalling inhibitor, was identified to be a target of miR-4261. MEG3 interacted with miR-4261, derepressed DKK2 and blocked the Wnt/β-catenin signalling, thereby inhibiting tumourigenesis and progression in ESCC. In vivo experiments also confirmed this conclusion. Our study for the first time elaborated the critical role of MEG3-miR-4261-DKK2-Wnt/β-catenin signalling axis in ESCC, and MEG3 could represent a novel diagnostic and prognostic biomarker and therapeutic target in ESCC.https://www.tandfonline.com/doi/10.1080/21691401.2019.1602538Esophageal squamous cell carcinomaLncRNA MEG3miR-4261Dickkopf-2Wnt/β-catenin signalling |
| spellingShingle | Ji Ma Teng-Fei Li Xin-Wei Han Hui-Feng Yuan Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling Artificial Cells, Nanomedicine, and Biotechnology Esophageal squamous cell carcinoma LncRNA MEG3 miR-4261 Dickkopf-2 Wnt/β-catenin signalling |
| title | Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling |
| title_full | Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling |
| title_fullStr | Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling |
| title_full_unstemmed | Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling |
| title_short | Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/β-catenin signalling |
| title_sort | downregulated meg3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with mir 4261 downregulating dkk2 and activating the wnt β catenin signalling |
| topic | Esophageal squamous cell carcinoma LncRNA MEG3 miR-4261 Dickkopf-2 Wnt/β-catenin signalling |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2019.1602538 |
| work_keys_str_mv | AT jima downregulatedmeg3contributestotumourprogressionandpoorprognosisinoesophagalsquamouscellcarcinomabyinteractingwithmir4261downregulatingdkk2andactivatingthewntbcateninsignalling AT tengfeili downregulatedmeg3contributestotumourprogressionandpoorprognosisinoesophagalsquamouscellcarcinomabyinteractingwithmir4261downregulatingdkk2andactivatingthewntbcateninsignalling AT xinweihan downregulatedmeg3contributestotumourprogressionandpoorprognosisinoesophagalsquamouscellcarcinomabyinteractingwithmir4261downregulatingdkk2andactivatingthewntbcateninsignalling AT huifengyuan downregulatedmeg3contributestotumourprogressionandpoorprognosisinoesophagalsquamouscellcarcinomabyinteractingwithmir4261downregulatingdkk2andactivatingthewntbcateninsignalling |