MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling
Chemoresistance is a severe clinical challenge in breast cancer. Hypoxia and cancer stem cells (CSCs) contribute to the paclitaxel (PTX) resistance, but the molecular mechanisms are still elusive. MicorRNAs (miRNA) have been considered a promising therapeutic strategy in various cancers. Here, we id...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-12-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.696269/full |
| _version_ | 1828143828982300672 |
|---|---|
| author | Jing-Hua Liu Wen-Ting Li Yue Yang Yan-Bo Qi Yu Cheng Jia-Hui Wu |
| author_facet | Jing-Hua Liu Wen-Ting Li Yue Yang Yan-Bo Qi Yu Cheng Jia-Hui Wu |
| author_sort | Jing-Hua Liu |
| collection | DOAJ |
| description | Chemoresistance is a severe clinical challenge in breast cancer. Hypoxia and cancer stem cells (CSCs) contribute to the paclitaxel (PTX) resistance, but the molecular mechanisms are still elusive. MicorRNAs (miRNA) have been considered a promising therapeutic strategy in various cancers. Here, we identified the crucial function of miR-526b-3p in regulating PTX resistance and CSC properties. Our data demonstrated that miR-526b-3p mimic repressed the cell viability of breast cancer cells. The counts of Edu-positive cells were reduced by miR-526b-3p in breast cancer cells. Meanwhile, the apoptosis of breast cancer cells was induced by miR-526b-3p. Tumorigenicity analysis in the nude mice confirmed that miR-526b-3p attenuated the breast cancer cell growth in vivo. Significantly, hypoxia could enhance IC50 value of PTX in breast cancer cells. IC50 value of PTX was induced in breast cancer mammospheres. The hypoxia-inducible factor 2α (HIF-2α) expression was enhanced, but miR-526b-3p expression was repressed under hypoxia in breast cancer cells. Also, breast cancer mammospheres presented high HIF-2α expression and low miR-526b-3p expression. The inhibition of miR-526b-3p enhanced the IC50 value of PTX in breast cancer cells. MiR-526b-3p inhibitor enhanced the colony formation counts of PTX-treated breast cancer cells. The treatment of miR-526b-3p mimic suppressed the sphere formation counts of breast cancer cells and inhibited ALDH1 and Nanog expression. MiR-526b-3p was able to target HIF-2α in the cells. The overexpression enhanced but miR-526b-3p reduced the IC50 value of PTX in breast cancer cells, in which the overexpression of HIF-2α could rescue the miR-526b-3p-inhibited IC50 value of PTX. Overexpression of HIF-2α reversed miR-526b-3p-regulated apoptosis, colony formation ability, and ALDH1 and Nanog expression in the cells. Interestingly, the overexpression of HIF-2α induced but miR-526b-3p repressed the expression of HIF-2α, Hey2, and Notch in PTX-treated breast cancer cells, while HIF-2α could reverse the effect of miR-526b-3p. In conclusion, miR-526b-3p attenuated breast cancer stem cell properties and chemoresistance by targeting HIF-2α/Notch signaling. MiR-526b-3p may be utilized in the relieving chemoresistance in breast cancer. |
| first_indexed | 2024-04-11T20:06:06Z |
| format | Article |
| id | doaj.art-ab1b9e0a0b304c41bde2e53cc18e4ed6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T20:06:06Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ab1b9e0a0b304c41bde2e53cc18e4ed62022-12-22T04:05:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.696269696269MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch SignalingJing-Hua Liu0Wen-Ting Li1Yue Yang2Yan-Bo Qi3Yu Cheng4Jia-Hui Wu5Department of General Practice, School of Public Health, Qiqihar Medical University, Qiqihar, ChinaScience Research Section, School of Public Health, Qiqihar Medical University, Qiqihar, ChinaTeaching and Research Section, School of Public Health, Qiqihar Medical University, Qiqihar, ChinaQiqihar Medical University, Qiqihar, ChinaDepartment of Nutrition and Food Hygiene, School of Public Health, Qiqihar Medical University, Qiqihar, ChinaDepartment of Environmental and Occupational Health, School of Public Health, Qiqihar Medical University, Qiqihar, ChinaChemoresistance is a severe clinical challenge in breast cancer. Hypoxia and cancer stem cells (CSCs) contribute to the paclitaxel (PTX) resistance, but the molecular mechanisms are still elusive. MicorRNAs (miRNA) have been considered a promising therapeutic strategy in various cancers. Here, we identified the crucial function of miR-526b-3p in regulating PTX resistance and CSC properties. Our data demonstrated that miR-526b-3p mimic repressed the cell viability of breast cancer cells. The counts of Edu-positive cells were reduced by miR-526b-3p in breast cancer cells. Meanwhile, the apoptosis of breast cancer cells was induced by miR-526b-3p. Tumorigenicity analysis in the nude mice confirmed that miR-526b-3p attenuated the breast cancer cell growth in vivo. Significantly, hypoxia could enhance IC50 value of PTX in breast cancer cells. IC50 value of PTX was induced in breast cancer mammospheres. The hypoxia-inducible factor 2α (HIF-2α) expression was enhanced, but miR-526b-3p expression was repressed under hypoxia in breast cancer cells. Also, breast cancer mammospheres presented high HIF-2α expression and low miR-526b-3p expression. The inhibition of miR-526b-3p enhanced the IC50 value of PTX in breast cancer cells. MiR-526b-3p inhibitor enhanced the colony formation counts of PTX-treated breast cancer cells. The treatment of miR-526b-3p mimic suppressed the sphere formation counts of breast cancer cells and inhibited ALDH1 and Nanog expression. MiR-526b-3p was able to target HIF-2α in the cells. The overexpression enhanced but miR-526b-3p reduced the IC50 value of PTX in breast cancer cells, in which the overexpression of HIF-2α could rescue the miR-526b-3p-inhibited IC50 value of PTX. Overexpression of HIF-2α reversed miR-526b-3p-regulated apoptosis, colony formation ability, and ALDH1 and Nanog expression in the cells. Interestingly, the overexpression of HIF-2α induced but miR-526b-3p repressed the expression of HIF-2α, Hey2, and Notch in PTX-treated breast cancer cells, while HIF-2α could reverse the effect of miR-526b-3p. In conclusion, miR-526b-3p attenuated breast cancer stem cell properties and chemoresistance by targeting HIF-2α/Notch signaling. MiR-526b-3p may be utilized in the relieving chemoresistance in breast cancer.https://www.frontiersin.org/articles/10.3389/fonc.2021.696269/fullbreast cancerhypoxiaCSCschemoresistancemiR-526b-3pHIF-2α |
| spellingShingle | Jing-Hua Liu Wen-Ting Li Yue Yang Yan-Bo Qi Yu Cheng Jia-Hui Wu MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling Frontiers in Oncology breast cancer hypoxia CSCs chemoresistance miR-526b-3p HIF-2α |
| title | MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling |
| title_full | MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling |
| title_fullStr | MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling |
| title_full_unstemmed | MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling |
| title_short | MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling |
| title_sort | mir 526b 3p attenuates breast cancer stem cell properties and chemoresistance by targeting hif 2α notch signaling |
| topic | breast cancer hypoxia CSCs chemoresistance miR-526b-3p HIF-2α |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.696269/full |
| work_keys_str_mv | AT jinghualiu mir526b3pattenuatesbreastcancerstemcellpropertiesandchemoresistancebytargetinghif2anotchsignaling AT wentingli mir526b3pattenuatesbreastcancerstemcellpropertiesandchemoresistancebytargetinghif2anotchsignaling AT yueyang mir526b3pattenuatesbreastcancerstemcellpropertiesandchemoresistancebytargetinghif2anotchsignaling AT yanboqi mir526b3pattenuatesbreastcancerstemcellpropertiesandchemoresistancebytargetinghif2anotchsignaling AT yucheng mir526b3pattenuatesbreastcancerstemcellpropertiesandchemoresistancebytargetinghif2anotchsignaling AT jiahuiwu mir526b3pattenuatesbreastcancerstemcellpropertiesandchemoresistancebytargetinghif2anotchsignaling |