ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner
Abstract Background Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. Methods In this study, we scr...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-024-01944-w |
| _version_ | 1797275603454394368 |
|---|---|
| author | Chuanpeng Zhang Ziyi Yu Susu Yang Yitao Liu Jiangni Song Juan Mao Minghui Li Yi Zhao |
| author_facet | Chuanpeng Zhang Ziyi Yu Susu Yang Yitao Liu Jiangni Song Juan Mao Minghui Li Yi Zhao |
| author_sort | Chuanpeng Zhang |
| collection | DOAJ |
| description | Abstract Background Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. Methods In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR. The biological role of circRPPH1 in TNBC was then verified by in vivo and in vitro experiments. Mechanistically, we verified the regulatory effects between circRPPH1 and ZNF460 and between circRPPH1 and miR-326 by chromatin immunoprecipitation (ChIP), fluorescence in situ hybridization assay, dual luciferase reporter gene assay and RNA pull-down assay. In addition, to determine the expression of associated proteins, we performed immunohistochemistry, immunofluorescence, and western blotting. Results The upregulation of circRPPH1 in TNBC was positively linked with a poor prognosis. Additionally, both in vivo and in vitro, circRPPH1 promoted the biologically malignant behavior of TNBC cells. Additionally, circRPPH1 may function as a molecular sponge for miR-326 to control integrin subunit alpha 5 (ITGA5) expression and activate the focal adhesion kinase (FAK)/PI3K/AKT pathway. Conclusion Our research showed that ZNF460 could promote circRPPH1 expression and that the circRPPH1/miR-326/ITGA5 axis could activate the FAK/PI3K/AKT pathway to promote the progression of TNBC. Therefore, circRPPH1 can be used as a therapeutic or diagnostic target for TNBC. |
| first_indexed | 2024-03-07T15:16:49Z |
| format | Article |
| id | doaj.art-283efab1c8944e60b3da9c07c4bc0cf0 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-03-07T15:16:49Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-283efab1c8944e60b3da9c07c4bc0cf02024-03-05T17:52:58ZengBMCMolecular Cancer1476-45982024-02-0123111610.1186/s12943-024-01944-wZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA mannerChuanpeng Zhang0Ziyi Yu1Susu Yang2Yitao Liu3Jiangni Song4Juan Mao5Minghui Li6Yi Zhao7Department of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. Methods In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR. The biological role of circRPPH1 in TNBC was then verified by in vivo and in vitro experiments. Mechanistically, we verified the regulatory effects between circRPPH1 and ZNF460 and between circRPPH1 and miR-326 by chromatin immunoprecipitation (ChIP), fluorescence in situ hybridization assay, dual luciferase reporter gene assay and RNA pull-down assay. In addition, to determine the expression of associated proteins, we performed immunohistochemistry, immunofluorescence, and western blotting. Results The upregulation of circRPPH1 in TNBC was positively linked with a poor prognosis. Additionally, both in vivo and in vitro, circRPPH1 promoted the biologically malignant behavior of TNBC cells. Additionally, circRPPH1 may function as a molecular sponge for miR-326 to control integrin subunit alpha 5 (ITGA5) expression and activate the focal adhesion kinase (FAK)/PI3K/AKT pathway. Conclusion Our research showed that ZNF460 could promote circRPPH1 expression and that the circRPPH1/miR-326/ITGA5 axis could activate the FAK/PI3K/AKT pathway to promote the progression of TNBC. Therefore, circRPPH1 can be used as a therapeutic or diagnostic target for TNBC.https://doi.org/10.1186/s12943-024-01944-wTNBCcircRPPH1miR-326ITGA5 |
| spellingShingle | Chuanpeng Zhang Ziyi Yu Susu Yang Yitao Liu Jiangni Song Juan Mao Minghui Li Yi Zhao ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner Molecular Cancer TNBC circRPPH1 miR-326 ITGA5 |
| title | ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner |
| title_full | ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner |
| title_fullStr | ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner |
| title_full_unstemmed | ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner |
| title_short | ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner |
| title_sort | znf460 mediated circrpph1 promotes tnbc progression through itga5 induced fak pi3k akt activation in a cerna manner |
| topic | TNBC circRPPH1 miR-326 ITGA5 |
| url | https://doi.org/10.1186/s12943-024-01944-w |
| work_keys_str_mv | AT chuanpengzhang znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT ziyiyu znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT susuyang znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT yitaoliu znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT jiangnisong znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT juanmao znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT minghuili znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner AT yizhao znf460mediatedcircrpph1promotestnbcprogressionthroughitga5inducedfakpi3kaktactivationinacernamanner |