MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma
Abstract Background MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-12-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-018-0694-9 |
| _version_ | 1819153351888076800 |
|---|---|
| author | Jun-feng Zhang Jian-shui Zhang Zhao-hua Zhao Peng-bo Yang Sheng-feng Ji Nan Li Qin-dong Shi Jing Tan Xi Xu Cang-bao Xu Ling-yu Zhao |
| author_facet | Jun-feng Zhang Jian-shui Zhang Zhao-hua Zhao Peng-bo Yang Sheng-feng Ji Nan Li Qin-dong Shi Jing Tan Xi Xu Cang-bao Xu Ling-yu Zhao |
| author_sort | Jun-feng Zhang |
| collection | DOAJ |
| description | Abstract Background MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated. Methods The expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene. Results We demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/β-catenin signaling pathway. Conclusions Our study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/β-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma. |
| first_indexed | 2024-12-22T15:03:49Z |
| format | Article |
| id | doaj.art-57815f2dda7a4636858e097f098f9956 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-22T15:03:49Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-57815f2dda7a4636858e097f098f99562022-12-21T18:22:03ZengBMCCancer Cell International1475-28672018-12-0118111310.1186/s12935-018-0694-9MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in gliomaJun-feng Zhang0Jian-shui Zhang1Zhao-hua Zhao2Peng-bo Yang3Sheng-feng Ji4Nan Li5Qin-dong Shi6Jing Tan7Xi Xu8Cang-bao Xu9Ling-yu Zhao10Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi’an Medical UniversityDepartment of Human Anatomy, Histology and Embryology, Xi’an Jiaotong University Health Science CenterDepartment of Human Anatomy, Xi’an Medical UniversityDepartment of Human Anatomy, Histology and Embryology, Xi’an Jiaotong University Health Science CenterDepartment of Human Anatomy, Histology and Embryology, Xi’an Jiaotong University Health Science CenterDepartment of Neuropathology, The First Affiliated Hospital of Xi’an Jiaotong UniversityThe First Affiliated Hospital of Xi’an Jiaotong UniversityThe First Affiliated Hospital of Xi’an Jiaotong UniversityShaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi’an Medical UniversityShaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi’an Medical UniversityDepartment of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science CenterAbstract Background MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated. Methods The expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene. Results We demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/β-catenin signaling pathway. Conclusions Our study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/β-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma.http://link.springer.com/article/10.1186/s12935-018-0694-9miR-770CDK8GliomaProliferationCell cycle |
| spellingShingle | Jun-feng Zhang Jian-shui Zhang Zhao-hua Zhao Peng-bo Yang Sheng-feng Ji Nan Li Qin-dong Shi Jing Tan Xi Xu Cang-bao Xu Ling-yu Zhao MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma Cancer Cell International miR-770 CDK8 Glioma Proliferation Cell cycle |
| title | MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma |
| title_full | MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma |
| title_fullStr | MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma |
| title_full_unstemmed | MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma |
| title_short | MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma |
| title_sort | microrna 770 affects proliferation and cell cycle transition by directly targeting cdk8 in glioma |
| topic | miR-770 CDK8 Glioma Proliferation Cell cycle |
| url | http://link.springer.com/article/10.1186/s12935-018-0694-9 |
| work_keys_str_mv | AT junfengzhang microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT jianshuizhang microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT zhaohuazhao microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT pengboyang microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT shengfengji microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT nanli microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT qindongshi microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT jingtan microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT xixu microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT cangbaoxu microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma AT lingyuzhao microrna770affectsproliferationandcellcycletransitionbydirectlytargetingcdk8inglioma |