MYBL2-induced PITPNA-AS1 upregulates SIK2 to exert oncogenic function in triple-negative breast cancer through miR-520d-5p and DDX54
| Autor: | Jianjin Guo, Yong Yang, Lianghui Wu, Pingbo Yao, Feng Xiao, Bolong Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
DDX54
Cell Cycle Proteins Triple Negative Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology Flow cytometry DEAD-box RNA Helicases Mice miR-520d-5p Downregulation and upregulation Western blot medicine Animals Humans Transcription factor SIK2 Triple-negative breast cancer Cell Proliferation Gene knockdown medicine.diagnostic_test Research PITPNA-AS1 General Medicine Neoplasm Proteins Antisense RNA Gene Expression Regulation Neoplastic MicroRNAs Apoptosis Disease Progression Trans-Activators Cancer research Medicine RNA Long Noncoding TNBC |
| Zdroj: | Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-17 (2021) Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| DOI: | 10.1186/s12967-021-02956-6 |
| Popis: | Background In recent years, long non-coding RNAs (lncRNAs) have attracted much attention because of its regulatory role in occurrence and progression of tumors, including triple-negative breast cancer (TNBC). LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) has been explored in some cancers, whereas its function and molecular mechanism in TNBC remain unclear. Methods PITPNA-AS1 expression in TNBC tissues and cells was determined by RT-qPCR. TNBC cell viability, proliferation, migration, invasion were assessed with CCK-8, colony formation, wound healing, transwell assays. Cell apoptosis was evaluated by flow cytometry. Expression of EMT-related markers was detected by western blot analyses. The molecular mechanism of PITPNA-AS1 was explored by RNA pull down, luciferase reporter, RIP and ChIP assays. Results PITPNA-AS1 showed high expression levels in TNBC tissues and cells. PITPNA-AS1 knockdown suppressed TNBC cell viability, proliferation, migration, invasion in vitro and inhibited xenograft tumor growth in mice. Mechanistically, PITPNA-AS1 upregulated SIK2 expression by sponging miR-520d-5p and recruiting DDX54 protein. Results of rescue assays suggested that the inhibitive effects of silenced PITPNA-AS1 on TNBC cellular processes were partially rescued by overexpressing SIK2 or combination of miR-520d-5p inhibition and DDX54 overexpression. More importantly, we found that the upregulation of PITPNA-AS1 in TNBC cells was attributed to transcription factor MYBL2. Conclusion PITPNA-AS1 activated by MYBL2 plays an oncogenic role in TNBC through upregulating SIK2. |
| Databáze: | OpenAIRE |
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