Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness
Abstract Background Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-025-02133-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585377121042432 |
|---|---|
| author | Oyku Ece Sumer Korbinian Schelzig Janine Jung Xiaoya Li Janina Moros Luisa Schwarzmüller Ezgi Sen Sabine Karolus Angelika Wörner Verônica Rodrigues de Melo Costa Nishanth Belugali Nataraj Efstathios-Iason Vlachavas Clarissa Gerhäuser Karin Müller-Decker Dominic Helm Yosef Yarden Birgitta Elisabeth Michels Cindy Körner |
| author_facet | Oyku Ece Sumer Korbinian Schelzig Janine Jung Xiaoya Li Janina Moros Luisa Schwarzmüller Ezgi Sen Sabine Karolus Angelika Wörner Verônica Rodrigues de Melo Costa Nishanth Belugali Nataraj Efstathios-Iason Vlachavas Clarissa Gerhäuser Karin Müller-Decker Dominic Helm Yosef Yarden Birgitta Elisabeth Michels Cindy Körner |
| author_sort | Oyku Ece Sumer |
| collection | DOAJ |
| description | Abstract Background Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet. Results Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism. Conclusions In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species. Graphical Abstract |
| format | Article |
| id | doaj-art-afa83e99425e4c00b3326d86febc127e |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-afa83e99425e4c00b3326d86febc127e2025-01-26T12:52:40ZengBMCBMC Biology1741-70072025-01-0123111910.1186/s12915-025-02133-xSelective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressivenessOyku Ece Sumer0Korbinian Schelzig1Janine Jung2Xiaoya Li3Janina Moros4Luisa Schwarzmüller5Ezgi Sen6Sabine Karolus7Angelika Wörner8Verônica Rodrigues de Melo Costa9Nishanth Belugali Nataraj10Efstathios-Iason Vlachavas11Clarissa Gerhäuser12Karin Müller-Decker13Dominic Helm14Yosef Yarden15Birgitta Elisabeth Michels16Cindy Körner17Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Department of Biological Regulation, Weizmann Institute of ScienceDivision of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Cancer Epigenomics, German Cancer Research Center (DKFZ)Tumor Models Core Facility, German Cancer Research Center (DKFZ)Proteomics Core Facility, German Cancer Research Center (DKFZ)Department of Biological Regulation, Weizmann Institute of ScienceDivision of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ)Abstract Background Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet. Results Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism. Conclusions In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species. Graphical Abstracthttps://doi.org/10.1186/s12915-025-02133-xBreast cancerAngiogenesismiRNAsIsomiRsmiR-1307miRNA arm switch |
| spellingShingle | Oyku Ece Sumer Korbinian Schelzig Janine Jung Xiaoya Li Janina Moros Luisa Schwarzmüller Ezgi Sen Sabine Karolus Angelika Wörner Verônica Rodrigues de Melo Costa Nishanth Belugali Nataraj Efstathios-Iason Vlachavas Clarissa Gerhäuser Karin Müller-Decker Dominic Helm Yosef Yarden Birgitta Elisabeth Michels Cindy Körner Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness BMC Biology Breast cancer Angiogenesis miRNAs IsomiRs miR-1307 miRNA arm switch |
| title | Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness |
| title_full | Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness |
| title_fullStr | Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness |
| title_full_unstemmed | Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness |
| title_short | Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness |
| title_sort | selective arm usage of pre mir 1307 dysregulates angiogenesis and affects breast cancer aggressiveness |
| topic | Breast cancer Angiogenesis miRNAs IsomiRs miR-1307 miRNA arm switch |
| url | https://doi.org/10.1186/s12915-025-02133-x |
| work_keys_str_mv | AT oykuecesumer selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT korbinianschelzig selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT janinejung selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT xiaoyali selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT janinamoros selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT luisaschwarzmuller selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT ezgisen selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT sabinekarolus selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT angelikaworner selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT veronicarodriguesdemelocosta selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT nishanthbelugalinataraj selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT efstathiosiasonvlachavas selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT clarissagerhauser selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT karinmullerdecker selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT dominichelm selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT yosefyarden selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT birgittaelisabethmichels selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness AT cindykorner selectivearmusageofpremir1307dysregulatesangiogenesisandaffectsbreastcanceraggressiveness |