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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2021
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oai:doaj.org-article:f7033f82393f4b86986a266ae648b40c2021-11-26T11:19:49ZlncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p2165-59792165-598710.1080/21655979.2021.2003928https://doaj.org/article/f7033f82393f4b86986a266ae648b40c2021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2003928https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Long 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.Jinfeng ZhangDonghua LiuGuoming DengQiuming WangLiang LiJinxiang ZhangHeming WuTaylor & Francis Grouparticletriple-negative breast cancermetastasislncrna pcat18activating transcription factor 7mir-103a-3pBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021) |
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triple-negative breast cancer metastasis lncrna pcat18 activating transcription factor 7 mir-103a-3p Biotechnology TP248.13-248.65 |
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triple-negative breast cancer metastasis lncrna pcat18 activating transcription factor 7 mir-103a-3p Biotechnology TP248.13-248.65 Jinfeng Zhang Donghua Liu Guoming Deng Qiuming Wang Liang Li Jinxiang Zhang Heming Wu lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p |
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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. |
format |
article |
author |
Jinfeng Zhang Donghua Liu Guoming Deng Qiuming Wang Liang Li Jinxiang Zhang Heming Wu |
author_facet |
Jinfeng Zhang Donghua Liu Guoming Deng Qiuming Wang Liang Li Jinxiang Zhang Heming Wu |
author_sort |
Jinfeng Zhang |
title |
lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p |
title_short |
lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p |
title_full |
lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p |
title_fullStr |
lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p |
title_full_unstemmed |
lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p |
title_sort |
lncrna prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging mir-103a-3p |
publisher |
Taylor & Francis Group |
publishDate |
2021 |
url |
https://doaj.org/article/f7033f82393f4b86986a266ae648b40c |
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