miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2
MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00108/full |
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| author | Balu Wu Guohong Liu Yanxia Jin Tian Yang Dongdong Zhang Lu Ding Fuling Zhou Yunbao Pan Yongchang Wei |
| author_facet | Balu Wu Guohong Liu Yanxia Jin Tian Yang Dongdong Zhang Lu Ding Fuling Zhou Yunbao Pan Yongchang Wei |
| author_sort | Balu Wu |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients. |
| first_indexed | 2024-12-23T21:01:20Z |
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| id | doaj.art-e169e1399bbb423d924a64b5d7e89209 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-23T21:01:20Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e169e1399bbb423d924a64b5d7e892092022-12-21T17:31:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00108503149miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2Balu Wu0Guohong Liu1Yanxia Jin2Tian Yang3Dongdong Zhang4Lu Ding5Fuling Zhou6Yunbao Pan7Yongchang Wei8Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Clinical Oncology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaMicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients.https://www.frontiersin.org/article/10.3389/fonc.2020.00108/fullbreast cancermicroRNAmiR-15b-5pHPSE2biomarker |
| spellingShingle | Balu Wu Guohong Liu Yanxia Jin Tian Yang Dongdong Zhang Lu Ding Fuling Zhou Yunbao Pan Yongchang Wei miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2 Frontiers in Oncology breast cancer microRNA miR-15b-5p HPSE2 biomarker |
| title | miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2 |
| title_full | miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2 |
| title_fullStr | miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2 |
| title_full_unstemmed | miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2 |
| title_short | miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2 |
| title_sort | mir 15b 5p promotes growth and metastasis in breast cancer by targeting hpse2 |
| topic | breast cancer microRNA miR-15b-5p HPSE2 biomarker |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00108/full |
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