miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9
Abstract This study is to explore the therapeutic effect and potential mechanisms of exosomal microRNAs (miRNAs) derived from the ovaries with primary ovarian insufficiency (POI). The POI mouse model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan. The apoptosis o...
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Wiley
2022-06-01
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Series: | Cancer Medicine |
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Online Access: | https://doi.org/10.1002/cam4.4615 |
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author | Xiujuan Zhang Ruihong Zhang Jing Hao Xiaoyan Huang Ming Liu Mengxiao Lv Chan Su Yu‐Lan Mu |
author_facet | Xiujuan Zhang Ruihong Zhang Jing Hao Xiaoyan Huang Ming Liu Mengxiao Lv Chan Su Yu‐Lan Mu |
author_sort | Xiujuan Zhang |
collection | DOAJ |
description | Abstract This study is to explore the therapeutic effect and potential mechanisms of exosomal microRNAs (miRNAs) derived from the ovaries with primary ovarian insufficiency (POI). The POI mouse model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan. The apoptosis of granulosa cells (GCs) incubated with exosomes extracted from ovarian tissues of control and POI groups was analyzed by flow cytometry. Then, high‐throughput sequencing was performed to detect the difference of miRNAs profile in ovarian tissue‐derived exosomes between the control and POI mice. The effect of differential miRNA on the apoptosis of CTX‐induced ovarian GCs was analyzed by flow cytometry. The results showed that POI mouse model was successfully established. Exosomes extracted from ovarian of normal and POI group have different effects on apoptosis of GCs induced by CTX. miRNA‐seq found that exosomal miR‐122‐5p in POI group increased significantly. miR‐122‐5p as the dominant miRNA targeting BCL9 was significantly upregulated in ovarian tissues of chemotherapy‐induced POI group. Exosomes derived from the ovaries in the control group and miR‐122‐5p inhibitor group attenuated the apoptosis of primary cultured ovarian GCs. In conclusion, exosomal miR‐122‐5p promoted the apoptosis of ovarian GCs by targeting BCL9, suggested that miR‐122‐5p may function as a potential target to restore ovarian function. |
first_indexed | 2024-12-11T22:53:56Z |
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id | doaj.art-74becf72c1fc41d4a20f817b989c2c9e |
institution | Directory Open Access Journal |
issn | 2045-7634 |
language | English |
last_indexed | 2024-12-11T22:53:56Z |
publishDate | 2022-06-01 |
publisher | Wiley |
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series | Cancer Medicine |
spelling | doaj.art-74becf72c1fc41d4a20f817b989c2c9e2022-12-22T00:47:20ZengWileyCancer Medicine2045-76342022-06-0111122414242610.1002/cam4.4615miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9Xiujuan Zhang0Ruihong Zhang1Jing Hao2Xiaoyan Huang3Ming Liu4Mengxiao Lv5Chan Su6Yu‐Lan Mu7Department of Gynecology and Obstetrics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan ChinaKey Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology School of Medicine, Shandong University Jinan ChinaKey Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology School of Medicine, Shandong University Jinan ChinaShandong Maternal and Child Health Care Hospital Jinan ChinaDepartment of Gynecology and Obstetrics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan ChinaShandong University of Traditional Chinese Medicine Jinan ChinaShandong University of Traditional Chinese Medicine Jinan ChinaDepartment of Gynecology and Obstetrics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan ChinaAbstract This study is to explore the therapeutic effect and potential mechanisms of exosomal microRNAs (miRNAs) derived from the ovaries with primary ovarian insufficiency (POI). The POI mouse model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan. The apoptosis of granulosa cells (GCs) incubated with exosomes extracted from ovarian tissues of control and POI groups was analyzed by flow cytometry. Then, high‐throughput sequencing was performed to detect the difference of miRNAs profile in ovarian tissue‐derived exosomes between the control and POI mice. The effect of differential miRNA on the apoptosis of CTX‐induced ovarian GCs was analyzed by flow cytometry. The results showed that POI mouse model was successfully established. Exosomes extracted from ovarian of normal and POI group have different effects on apoptosis of GCs induced by CTX. miRNA‐seq found that exosomal miR‐122‐5p in POI group increased significantly. miR‐122‐5p as the dominant miRNA targeting BCL9 was significantly upregulated in ovarian tissues of chemotherapy‐induced POI group. Exosomes derived from the ovaries in the control group and miR‐122‐5p inhibitor group attenuated the apoptosis of primary cultured ovarian GCs. In conclusion, exosomal miR‐122‐5p promoted the apoptosis of ovarian GCs by targeting BCL9, suggested that miR‐122‐5p may function as a potential target to restore ovarian function.https://doi.org/10.1002/cam4.4615BCL9exosomemiR‐122‐5povarian granulosa cellpremature ovarian insufficiency |
spellingShingle | Xiujuan Zhang Ruihong Zhang Jing Hao Xiaoyan Huang Ming Liu Mengxiao Lv Chan Su Yu‐Lan Mu miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9 Cancer Medicine BCL9 exosome miR‐122‐5p ovarian granulosa cell premature ovarian insufficiency |
title | miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9 |
title_full | miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9 |
title_fullStr | miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9 |
title_full_unstemmed | miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9 |
title_short | miRNA‐122‐5p in POI ovarian‐derived exosomes promotes granulosa cell apoptosis by regulating BCL9 |
title_sort | mirna 122 5p in poi ovarian derived exosomes promotes granulosa cell apoptosis by regulating bcl9 |
topic | BCL9 exosome miR‐122‐5p ovarian granulosa cell premature ovarian insufficiency |
url | https://doi.org/10.1002/cam4.4615 |
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