IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p
Abstract Background Long noncoding RNAs (LncRNAs) represent a class of widespread and diverse endogenous RNAs that can posttranscriptionally regulate gene expression through the interaction with RNA-binding proteins and micro RNAs (miRNAs). Here, we report that in breast carcinoma cells, the insulin...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-018-0959-1 |
| _version_ | 1818656932871798784 |
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| author | Yanchun Zhou Xiuhua Meng Shaoying Chen Wei Li Delin Li Robert Singer Wei Gu |
| author_facet | Yanchun Zhou Xiuhua Meng Shaoying Chen Wei Li Delin Li Robert Singer Wei Gu |
| author_sort | Yanchun Zhou |
| collection | DOAJ |
| description | Abstract Background Long noncoding RNAs (LncRNAs) represent a class of widespread and diverse endogenous RNAs that can posttranscriptionally regulate gene expression through the interaction with RNA-binding proteins and micro RNAs (miRNAs). Here, we report that in breast carcinoma cells, the insulin-like growth factor 2 messenger RNA binding protein (IMP1) binds to lncRNA urethral carcinoma-associated 1 (UCA1) and suppresses the UCA1-induced invasive phenotype. Methods RT-qPCR and RNA sequence assays were used to investigate the expression of UCA1 and miRNAs in breast cancer cells in response to IMP1 expression. The role of IMP1-UCA1 interaction in cell invasion was demonstrated by transwell analysis through loss-of-function and gain-of-function effects. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular interactions of IMP1-UCA1 and UCA1-miR-122-5p involved in breast cancer cells. Results In breast cancer cells, IMP1 interacts with UCA1 via the “ACACCC” motifs within UCA1 and destabilizes UCA1 through the recruitment of CCR4-NOT1 deadenylase complex. Meanwhile, binding of IMP1 prevents the association of miR-122-5p with UCA1, thereby shifting the availability of miR-122-5p from UCA1 to the target mRNAs and reducing the UCA1-mediated cell invasion. Accordingly, either IMP1 silencing or UCA1 overexpression resulted in reduced levels of free miR-122-5p within the cytoplasm, affecting miR-122-5p in regulating its target mRNAs. Conclusions Our study provides initial evidence that interaction between IMP1 and UCA1 enhances UCA1 decay and competes for miR-122-5p binding, leading to the liberation of miR-122-5p activity and the reduction of cell invasiveness. |
| first_indexed | 2024-12-17T03:33:27Z |
| format | Article |
| id | doaj.art-e52dddfc95f94e83be7d8153bd5d80c0 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-17T03:33:27Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-e52dddfc95f94e83be7d8153bd5d80c02022-12-21T22:05:12ZengBMCBreast Cancer Research1465-542X2018-04-0120111510.1186/s13058-018-0959-1IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5pYanchun Zhou0Xiuhua Meng1Shaoying Chen2Wei Li3Delin Li4Robert Singer5Wei Gu6Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical CollegeDepartment of Anatomy and Structural Biology, Albert Einstein College of MedicineDepartment of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical CollegeDepartment of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical CollegeDepartment of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical CollegeDepartment of Anatomy and Structural Biology, Albert Einstein College of MedicineDepartment of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical CollegeAbstract Background Long noncoding RNAs (LncRNAs) represent a class of widespread and diverse endogenous RNAs that can posttranscriptionally regulate gene expression through the interaction with RNA-binding proteins and micro RNAs (miRNAs). Here, we report that in breast carcinoma cells, the insulin-like growth factor 2 messenger RNA binding protein (IMP1) binds to lncRNA urethral carcinoma-associated 1 (UCA1) and suppresses the UCA1-induced invasive phenotype. Methods RT-qPCR and RNA sequence assays were used to investigate the expression of UCA1 and miRNAs in breast cancer cells in response to IMP1 expression. The role of IMP1-UCA1 interaction in cell invasion was demonstrated by transwell analysis through loss-of-function and gain-of-function effects. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular interactions of IMP1-UCA1 and UCA1-miR-122-5p involved in breast cancer cells. Results In breast cancer cells, IMP1 interacts with UCA1 via the “ACACCC” motifs within UCA1 and destabilizes UCA1 through the recruitment of CCR4-NOT1 deadenylase complex. Meanwhile, binding of IMP1 prevents the association of miR-122-5p with UCA1, thereby shifting the availability of miR-122-5p from UCA1 to the target mRNAs and reducing the UCA1-mediated cell invasion. Accordingly, either IMP1 silencing or UCA1 overexpression resulted in reduced levels of free miR-122-5p within the cytoplasm, affecting miR-122-5p in regulating its target mRNAs. Conclusions Our study provides initial evidence that interaction between IMP1 and UCA1 enhances UCA1 decay and competes for miR-122-5p binding, leading to the liberation of miR-122-5p activity and the reduction of cell invasiveness.http://link.springer.com/article/10.1186/s13058-018-0959-1lncRNARNA-binding proteinIMP1UCA1IMP1-UCA1 interactionUCA1-miR122-5p interaction |
| spellingShingle | Yanchun Zhou Xiuhua Meng Shaoying Chen Wei Li Delin Li Robert Singer Wei Gu IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p Breast Cancer Research lncRNA RNA-binding protein IMP1 UCA1 IMP1-UCA1 interaction UCA1-miR122-5p interaction |
| title | IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p |
| title_full | IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p |
| title_fullStr | IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p |
| title_full_unstemmed | IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p |
| title_short | IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p |
| title_sort | imp1 regulates uca1 mediated cell invasion through facilitating uca1 decay and decreasing the sponge effect of uca1 for mir 122 5p |
| topic | lncRNA RNA-binding protein IMP1 UCA1 IMP1-UCA1 interaction UCA1-miR122-5p interaction |
| url | http://link.springer.com/article/10.1186/s13058-018-0959-1 |
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