LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer
Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2‐1‐AS1 (NKX2‐1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12911 |
| _version_ | 1818380339133808640 |
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| author | Fei Teng Ju‐Xiang Zhang Yi Chen Xiao‐Dong Shen Chang Su Yan‐Jiao Guo Pu‐Hua Wang Chen‐cheng Shi Ming Lei Yi‐Ou Cao Shao‐Qun Liu |
| author_facet | Fei Teng Ju‐Xiang Zhang Yi Chen Xiao‐Dong Shen Chang Su Yan‐Jiao Guo Pu‐Hua Wang Chen‐cheng Shi Ming Lei Yi‐Ou Cao Shao‐Qun Liu |
| author_sort | Fei Teng |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2‐1‐AS1 (NKX2‐1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2‐1‐AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2‐1‐AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT‐PCR). Using loss‐of‐function and gain‐of‐function experiments, the biological functions of NKX2‐1‐AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2‐1‐AS1 regulates angiogenic processes, tube formation and co‐culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual‐luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2‐1‐AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2‐1‐AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2‐1‐AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2‐1‐AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual‐luciferase assays revealed that the microRNA miR‐145‐5p is a direct target of NKX2‐1‐AS1 and that NKX2‐1‐AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR‐145‐5p; besides, the NKX2‐1‐AS1/miR‐145‐5p axis induces the translation of SERPINE1, thus activating the VEGFR‐2 signaling pathway to promote tumor progression and angiogenesis. NKX2‐1‐AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2‐1‐AS1 functions as a ceRNA to miR‐145‐5p and promotes tumor progression and angiogenesis by activating the VEGFR‐2 signaling pathway via SERPINE1. |
| first_indexed | 2024-12-14T02:17:06Z |
| format | Article |
| id | doaj.art-72e669218a2d42028d179aa1b7ba0e26 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-14T02:17:06Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-72e669218a2d42028d179aa1b7ba0e262022-12-21T23:20:36ZengWileyMolecular Oncology1574-78911878-02612021-04-011541234125510.1002/1878-0261.12911LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancerFei Teng0Ju‐Xiang Zhang1Yi Chen2Xiao‐Dong Shen3Chang Su4Yan‐Jiao Guo5Pu‐Hua Wang6Chen‐cheng Shi7Ming Lei8Yi‐Ou Cao9Shao‐Qun Liu10Department of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaShanghai Med‐X Engineering Center for Medical Equipment and Technology School of Biomedical Engineering Shanghai Jiao Tong University ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaDepartment of Gastrointestinal Surgery Minhang HospitalFudan University Shanghai ChinaLong noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2‐1‐AS1 (NKX2‐1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2‐1‐AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2‐1‐AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT‐PCR). Using loss‐of‐function and gain‐of‐function experiments, the biological functions of NKX2‐1‐AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2‐1‐AS1 regulates angiogenic processes, tube formation and co‐culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual‐luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2‐1‐AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2‐1‐AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2‐1‐AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2‐1‐AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual‐luciferase assays revealed that the microRNA miR‐145‐5p is a direct target of NKX2‐1‐AS1 and that NKX2‐1‐AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR‐145‐5p; besides, the NKX2‐1‐AS1/miR‐145‐5p axis induces the translation of SERPINE1, thus activating the VEGFR‐2 signaling pathway to promote tumor progression and angiogenesis. NKX2‐1‐AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2‐1‐AS1 functions as a ceRNA to miR‐145‐5p and promotes tumor progression and angiogenesis by activating the VEGFR‐2 signaling pathway via SERPINE1.https://doi.org/10.1002/1878-0261.12911gastric cancercompeting endogenous RNAserpin family E member 1VEGFR‐2 signaling pathwayNKX2‐1 antisense RNA 1 |
| spellingShingle | Fei Teng Ju‐Xiang Zhang Yi Chen Xiao‐Dong Shen Chang Su Yan‐Jiao Guo Pu‐Hua Wang Chen‐cheng Shi Ming Lei Yi‐Ou Cao Shao‐Qun Liu LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer Molecular Oncology gastric cancer competing endogenous RNA serpin family E member 1 VEGFR‐2 signaling pathway NKX2‐1 antisense RNA 1 |
| title | LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer |
| title_full | LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer |
| title_fullStr | LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer |
| title_full_unstemmed | LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer |
| title_short | LncRNA NKX2‐1‐AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR‐2 signaling pathway in gastric cancer |
| title_sort | lncrna nkx2 1 as1 promotes tumor progression and angiogenesis via upregulation of serpine1 expression and activation of the vegfr 2 signaling pathway in gastric cancer |
| topic | gastric cancer competing endogenous RNA serpin family E member 1 VEGFR‐2 signaling pathway NKX2‐1 antisense RNA 1 |
| url | https://doi.org/10.1002/1878-0261.12911 |
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