lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p
Long non-coding RNA (lncRNA) prostate cancer-associated transcript 18 (PCAT18) is a potential diagnostic target for adenocarcinoma. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. Based on data from an online database, a significant decline in lncRNA PCAT18 was obs...
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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Taylor & Francis Group
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/f7033f82393f4b86986a266ae648b40c |
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| Sumario: | Long non-coding RNA (lncRNA) prostate cancer-associated transcript 18 (PCAT18) is a potential diagnostic target for adenocarcinoma. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. Based on data from an online database, a significant decline in lncRNA PCAT18 was observed in patients with TNBC subtype compared to a population with normal breast tissue. Patients with TNBC with high PCAT18 levels presented good outcomes. Patients with TNBC with high PCAT18 had a lower rate of lymph node-positive metastasis than those with low PCAT18. PCAT18-upregulation inhibited, while PCAT18-downregulation promoted, migration and expression of matrix metalloproteinases 9/2 (MMP9/MMP2) and uridylyl phosphate adenosine (uPA) in TNBC cells. Activating transcription factor 7 (ATF7) was positively associated with PCAT18, and ATF7-inhibition abrogated the anti-migration effects of PCAT18 on TNBC cells. Mechanistically, miR-103a-3p directly targeted and inhibited ATF7 expression. PCAT18 competitively sponges miR-103a-3p, promoting the expression of ATF7. Exogenous PCAT18 was associated with lower incidence of lung metastasis followed by the upregulation of ATF7, which was prevented by the treatment of miR-103a-3p mimics. Collectively, PCAT18 was expressed at low levels in TNBC, and PCAT18 could sponge miR-103a-3p and promote ATF7 expression, resulting in prevention of TNBC metastasis. Thus, PCAT18 can serve as a predictive factor for patients with metastatic TNBC. Graphical abstract: Graphi cal abstract: In Triple-Negative Breast Cancer Cells, lncRNA PCAT18 is lowly expressed. The reduced PCAT18 limited the binding of PCAT18 to miR-103a-3p, resulting in an increase of miR-103a-3p. Subsequently, miR-103a-3p directly binds to the 3ʹUTR of the ATF7 gene to reduce the expression of ATF7, followed by an increase in MMP9/2 and uPA, resulting in progression of tumor metastasis. |
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