TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway
Abstract Background Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells. Methods Fluorescence in situ hybridization and quantitative real-time PCR were conducted to...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-02-01
|
| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-017-0422-2 |
| _version_ | 1818264081236230144 |
|---|---|
| author | Jian Zheng Xiaobai Liu Yixue Xue Wei Gong Jun Ma Zhuo Xi Zhongyou Que Yunhui Liu |
| author_facet | Jian Zheng Xiaobai Liu Yixue Xue Wei Gong Jun Ma Zhuo Xi Zhongyou Que Yunhui Liu |
| author_sort | Jian Zheng |
| collection | DOAJ |
| description | Abstract Background Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells. Methods Fluorescence in situ hybridization and quantitative real-time PCR were conducted to profile the cell distribution and expression of circ-TTBK2 and microRNA-217 (miR-217) in glioma tissues and cells. Immunohistochemical and western blot were used to determine the expression of HNF1β and Derlin-1 in glioma tissues and cells. Stable knockdown of circ-TTBK2 or overexpression of miR-217 glioma cell lines (U87 and U251) were established to explore the function of circ-TTBK2 and miR-217 in glioma cells. Further, luciferase reports and RNA immunoprecipitation were used to investigate the correlation between circ-TTBK2 and miR-217. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate circ-TTBK2 and miR-217 function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between HNF1β and Derlin-1. Results We found that circ-TTBK2 was upregulated in glioma tissues and cell lines, while linear TTBK2 was not dysregulated in glioma tissues and cells. Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis. MiR-217 was downregulated in glioma tissues and cell lines. We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1β was a direct target of miR-217, and played oncogenic role in glioma cells. Remarkably, circ-TTBK2 knockdown combined with miR-217 overexpression led to tumor regression in vivo. Conclusions These results demonstrated a novel role circ-TTBK2 in the glioma progression. |
| first_indexed | 2024-12-12T19:29:14Z |
| format | Article |
| id | doaj.art-648cb9d349954c00b142118471193953 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-12T19:29:14Z |
| publishDate | 2017-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-648cb9d349954c00b1421184711939532022-12-22T00:14:28ZengBMCJournal of Hematology & Oncology1756-87222017-02-0110111910.1186/s13045-017-0422-2TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathwayJian Zheng0Xiaobai Liu1Yixue Xue2Wei Gong3Jun Ma4Zhuo Xi5Zhongyou Que6Yunhui Liu7Department of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityAbstract Background Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells. Methods Fluorescence in situ hybridization and quantitative real-time PCR were conducted to profile the cell distribution and expression of circ-TTBK2 and microRNA-217 (miR-217) in glioma tissues and cells. Immunohistochemical and western blot were used to determine the expression of HNF1β and Derlin-1 in glioma tissues and cells. Stable knockdown of circ-TTBK2 or overexpression of miR-217 glioma cell lines (U87 and U251) were established to explore the function of circ-TTBK2 and miR-217 in glioma cells. Further, luciferase reports and RNA immunoprecipitation were used to investigate the correlation between circ-TTBK2 and miR-217. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate circ-TTBK2 and miR-217 function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between HNF1β and Derlin-1. Results We found that circ-TTBK2 was upregulated in glioma tissues and cell lines, while linear TTBK2 was not dysregulated in glioma tissues and cells. Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis. MiR-217 was downregulated in glioma tissues and cell lines. We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1β was a direct target of miR-217, and played oncogenic role in glioma cells. Remarkably, circ-TTBK2 knockdown combined with miR-217 overexpression led to tumor regression in vivo. Conclusions These results demonstrated a novel role circ-TTBK2 in the glioma progression.http://link.springer.com/article/10.1186/s13045-017-0422-2Circular RNAscirc-TTBK2MicroRNAsmiR-217Glioma |
| spellingShingle | Jian Zheng Xiaobai Liu Yixue Xue Wei Gong Jun Ma Zhuo Xi Zhongyou Que Yunhui Liu TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway Journal of Hematology & Oncology Circular RNAs circ-TTBK2 MicroRNAs miR-217 Glioma |
| title | TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway |
| title_full | TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway |
| title_fullStr | TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway |
| title_full_unstemmed | TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway |
| title_short | TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway |
| title_sort | ttbk2 circular rna promotes glioma malignancy by regulating mir 217 hnf1β derlin 1 pathway |
| topic | Circular RNAs circ-TTBK2 MicroRNAs miR-217 Glioma |
| url | http://link.springer.com/article/10.1186/s13045-017-0422-2 |
| work_keys_str_mv | AT jianzheng ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT xiaobailiu ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT yixuexue ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT weigong ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT junma ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT zhuoxi ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT zhongyouque ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway AT yunhuiliu ttbk2circularrnapromotesgliomamalignancybyregulatingmir217hnf1bderlin1pathway |