LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization
Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study,...
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Published in | Oncogene Vol. 43; no. 14; pp. 1019 - 1032 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Nature Publishing Group
28.03.2024
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Abstract | Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer. |
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AbstractList | Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer. |
Author | Luo, Dan Jin, Yuhan Chen, Bing Wang, Yajie Yang, Qifeng Kong, Xiaoli Li, Yaming Long, Li Wang, Lijuan Zhao, Wenjing Xu, Fanchao Wang, Lei Ye, Fangzhou Su, Peng Liang, Yiran |
Author_xml | – sequence: 1 givenname: Yiran surname: Liang fullname: Liang, Yiran organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 2 givenname: Bing surname: Chen fullname: Chen, Bing organization: Biological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 3 givenname: Fanchao surname: Xu fullname: Xu, Fanchao organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 4 givenname: Li surname: Long fullname: Long, Li organization: Department of Breast Surgery, Mianyang Central Hospital, Mianyang, Sichuan, 621000, P.R. China – sequence: 5 givenname: Fangzhou surname: Ye fullname: Ye, Fangzhou organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 6 givenname: Yajie surname: Wang fullname: Wang, Yajie organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 7 givenname: Dan surname: Luo fullname: Luo, Dan organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 8 givenname: Yaming surname: Li fullname: Li, Yaming organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 9 givenname: Wenjing surname: Zhao fullname: Zhao, Wenjing organization: Biological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 10 givenname: Lijuan surname: Wang fullname: Wang, Lijuan organization: Biological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 11 givenname: Yuhan surname: Jin fullname: Jin, Yuhan organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 12 givenname: Lei surname: Wang fullname: Wang, Lei organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 13 givenname: Xiaoli surname: Kong fullname: Kong, Xiaoli organization: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China – sequence: 14 givenname: Peng orcidid: 0000-0002-7000-0474 surname: Su fullname: Su, Peng email: supeng820125@163.com organization: Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, P.R. China. supeng820125@163.com – sequence: 15 givenname: Qifeng orcidid: 0000-0003-0576-8513 surname: Yang fullname: Yang, Qifeng email: qifengy_sdu@163.com, qifengy_sdu@163.com, qifengy_sdu@163.com organization: Research Institute of Breast Cancer, Shandong University, Jinan, Shandong, 250012, P.R. China. qifengy_sdu@163.com |
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Snippet | Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the... |
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SubjectTerms | Argonaute 2 protein Autophagy Autophagy - genetics Breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Cell Proliferation Cytoplasm Female Gene Expression Regulation, Neoplastic Humans MicroRNAs - genetics Molecular modelling mRNA Non-coding RNA Poly(A)-Binding Protein I - genetics Poly(A)-Binding Protein I - metabolism RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism RNA, Messenger - genetics RNA-Binding Proteins - genetics RNA-induced silencing complex RNA-mediated interference Therapeutic targets |
Title | LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization |
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