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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Main Authors: Xiujuan Zhang, Ruihong Zhang, Jing Hao, Xiaoyan Huang, Ming Liu, Mengxiao Lv, Chan Su, Yu‐Lan Mu
Format: Article
Language:English
Published: Wiley 2022-06-01
Series:Cancer Medicine
Subjects:
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.
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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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