Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer
BackgroundRecently, multiple lines of evidence have demonstrated that linc00662 serves as an oncogene in various cancers. However, the exact mechanism of oncogenesis mediated by linc00662 in colorectal cancer (CRC) remains unknown. In this study, we aimed to explore the biological role of linc00662...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-01-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.01385/full |
| _version_ | 1811198633759997952 |
|---|---|
| author | Huaiming Wang Huaiming Wang Huaiming Wang Mengya Yu Mengya Yu Weixian Hu Weixian Hu Xin Chen Xin Chen Yuwen Luo Yuwen Luo Xiaosheng Lin Yongming Zeng Xueqing Yao Xueqing Yao |
| author_facet | Huaiming Wang Huaiming Wang Huaiming Wang Mengya Yu Mengya Yu Weixian Hu Weixian Hu Xin Chen Xin Chen Yuwen Luo Yuwen Luo Xiaosheng Lin Yongming Zeng Xueqing Yao Xueqing Yao |
| author_sort | Huaiming Wang |
| collection | DOAJ |
| description | BackgroundRecently, multiple lines of evidence have demonstrated that linc00662 serves as an oncogene in various cancers. However, the exact mechanism of oncogenesis mediated by linc00662 in colorectal cancer (CRC) remains unknown. In this study, we aimed to explore the biological role of linc00662 in the regulation of CRC progression.MethodsBoth gene expression omnibus (GEO) and the cancer genome atlas (TCGA) datasets were used to evaluate the expression of linc00662. RT-qPCR was used to analyze the expression of linc00662, miR-497-5p, and AVL9 in CRC clinical samples and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assay, and xenograft model were used to investigate the effect of linc00662 on CRC cell proliferation, cell cycle, and metastasis. Western blot analysis was used to analyze the expression of the epithelial-mesenchymal transition (EMT)-associated markers. Furthermore, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. Dual-luciferase reporter assays were used to analyze the regulatory relationships among linc00662, miR-497-5p, and AVL9.ResultsIn this study, we found that the expression of linc00662 was significantly upregulated in CRC tissues compared to normal tissues and positively correlated with tissue differentiation, T stage, and lymphatic metastasis. Further, our data showed that the expression of linc00662 was positively associated with lymph node metastasis, TMN stage, and poor-moderate differentiation. Patients with higher linc00662 expression level were more likely to have poorer overall survival. Knockdown of linc00662 inhibited CRC cell growth, induced cell apoptosis, triggered cell cycle arrest at G2/M phase, and suppressed cell migration and invasion through regulating the EMT pathway. Further, mechanistic studies revealed that knockdown of linc00662 significantly reduced the expression of AVL9, a direct target of miR-497-5p.ConclusionsLinc00662 was significantly upregulated in CRC, and mediated CRC progression and metastasis by competing with miR-497-5p to modulate the expression of AVL9. Therefore, our result sheds light on the potential application of linc00662 in CRC diagnosis and therapy. |
| first_indexed | 2024-04-12T01:34:35Z |
| format | Article |
| id | doaj.art-e633aa204c8b4c93b1e87349b7a9d2c7 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T01:34:35Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-e633aa204c8b4c93b1e87349b7a9d2c72022-12-22T03:53:22ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-01-011010.3389/fgene.2019.01385487689Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal CancerHuaiming Wang0Huaiming Wang1Huaiming Wang2Mengya Yu3Mengya Yu4Weixian Hu5Weixian Hu6Xin Chen7Xin Chen8Yuwen Luo9Yuwen Luo10Xiaosheng Lin11Yongming Zeng12Xueqing Yao13Xueqing Yao14The Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaBackgroundRecently, multiple lines of evidence have demonstrated that linc00662 serves as an oncogene in various cancers. However, the exact mechanism of oncogenesis mediated by linc00662 in colorectal cancer (CRC) remains unknown. In this study, we aimed to explore the biological role of linc00662 in the regulation of CRC progression.MethodsBoth gene expression omnibus (GEO) and the cancer genome atlas (TCGA) datasets were used to evaluate the expression of linc00662. RT-qPCR was used to analyze the expression of linc00662, miR-497-5p, and AVL9 in CRC clinical samples and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assay, and xenograft model were used to investigate the effect of linc00662 on CRC cell proliferation, cell cycle, and metastasis. Western blot analysis was used to analyze the expression of the epithelial-mesenchymal transition (EMT)-associated markers. Furthermore, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. Dual-luciferase reporter assays were used to analyze the regulatory relationships among linc00662, miR-497-5p, and AVL9.ResultsIn this study, we found that the expression of linc00662 was significantly upregulated in CRC tissues compared to normal tissues and positively correlated with tissue differentiation, T stage, and lymphatic metastasis. Further, our data showed that the expression of linc00662 was positively associated with lymph node metastasis, TMN stage, and poor-moderate differentiation. Patients with higher linc00662 expression level were more likely to have poorer overall survival. Knockdown of linc00662 inhibited CRC cell growth, induced cell apoptosis, triggered cell cycle arrest at G2/M phase, and suppressed cell migration and invasion through regulating the EMT pathway. Further, mechanistic studies revealed that knockdown of linc00662 significantly reduced the expression of AVL9, a direct target of miR-497-5p.ConclusionsLinc00662 was significantly upregulated in CRC, and mediated CRC progression and metastasis by competing with miR-497-5p to modulate the expression of AVL9. Therefore, our result sheds light on the potential application of linc00662 in CRC diagnosis and therapy.https://www.frontiersin.org/article/10.3389/fgene.2019.01385/fullcolorectal cancer (CRC)linc00662biomarkerproliferationprognosis |
| spellingShingle | Huaiming Wang Huaiming Wang Huaiming Wang Mengya Yu Mengya Yu Weixian Hu Weixian Hu Xin Chen Xin Chen Yuwen Luo Yuwen Luo Xiaosheng Lin Yongming Zeng Xueqing Yao Xueqing Yao Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer Frontiers in Genetics colorectal cancer (CRC) linc00662 biomarker proliferation prognosis |
| title | Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer |
| title_full | Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer |
| title_fullStr | Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer |
| title_full_unstemmed | Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer |
| title_short | Linc00662 Promotes Tumorigenesis and Progression by Regulating miR-497-5p/AVL9 Axis in Colorectal Cancer |
| title_sort | linc00662 promotes tumorigenesis and progression by regulating mir 497 5p avl9 axis in colorectal cancer |
| topic | colorectal cancer (CRC) linc00662 biomarker proliferation prognosis |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.01385/full |
| work_keys_str_mv | AT huaimingwang linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT huaimingwang linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT huaimingwang linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT mengyayu linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT mengyayu linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT weixianhu linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT weixianhu linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT xinchen linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT xinchen linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT yuwenluo linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT yuwenluo linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT xiaoshenglin linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT yongmingzeng linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT xueqingyao linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer AT xueqingyao linc00662promotestumorigenesisandprogressionbyregulatingmir4975pavl9axisincolorectalcancer |