The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs
Abstract Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | Molecular Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12943-019-1032-0 |
| _version_ | 1818996177989795840 |
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| author | Chao-Jie Wang Chun-Chao Zhu Jia Xu Ming Wang Wen-Yi Zhao Qiang Liu Gang Zhao Zi-Zhen Zhang |
| author_facet | Chao-Jie Wang Chun-Chao Zhu Jia Xu Ming Wang Wen-Yi Zhao Qiang Liu Gang Zhao Zi-Zhen Zhang |
| author_sort | Chao-Jie Wang |
| collection | DOAJ |
| description | Abstract Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo. Results UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model. Conclusions UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment. |
| first_indexed | 2024-12-20T21:25:36Z |
| format | Article |
| id | doaj.art-ee6fb104778948bc9014fe573397dfe8 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-20T21:25:36Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-ee6fb104778948bc9014fe573397dfe82022-12-21T19:26:10ZengBMCMolecular Cancer1476-45982019-07-0118111210.1186/s12943-019-1032-0The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAsChao-Jie Wang0Chun-Chao Zhu1Jia Xu2Ming Wang3Wen-Yi Zhao4Qiang Liu5Gang Zhao6Zi-Zhen Zhang7Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo. Results UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model. Conclusions UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment.http://link.springer.com/article/10.1186/s12943-019-1032-0lncRNAUCA1Gastric cancermiRNAPDL1 |
| spellingShingle | Chao-Jie Wang Chun-Chao Zhu Jia Xu Ming Wang Wen-Yi Zhao Qiang Liu Gang Zhao Zi-Zhen Zhang The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs Molecular Cancer lncRNA UCA1 Gastric cancer miRNA PDL1 |
| title | The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs |
| title_full | The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs |
| title_fullStr | The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs |
| title_full_unstemmed | The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs |
| title_short | The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs |
| title_sort | lncrna uca1 promotes proliferation migration immune escape and inhibits apoptosis in gastric cancer by sponging anti tumor mirnas |
| topic | lncRNA UCA1 Gastric cancer miRNA PDL1 |
| url | http://link.springer.com/article/10.1186/s12943-019-1032-0 |
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