RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells
Abstract Background We elucidated the role of specific MicroRNAs (miRNAs) in the development of polycystic ovary syndrome (PCOS) and explained the changes in the proliferation of granulosa cells. Excised ovarian cortex specimens were collected for miRNA profiling analysis (n = 20 PCOS females and 5...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-020-0611-4 |
| _version_ | 1797863845032624128 |
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| author | Zhengfang Xiong Bing Li Wenjuan Wang Xianghui Zeng Binye Li Shengyan Jian Liyun Wang |
| author_facet | Zhengfang Xiong Bing Li Wenjuan Wang Xianghui Zeng Binye Li Shengyan Jian Liyun Wang |
| author_sort | Zhengfang Xiong |
| collection | DOAJ |
| description | Abstract Background We elucidated the role of specific MicroRNAs (miRNAs) in the development of polycystic ovary syndrome (PCOS) and explained the changes in the proliferation of granulosa cells. Excised ovarian cortex specimens were collected for miRNA profiling analysis (n = 20 PCOS females and 5 non-PCOS females). Insulin-treated ovarian granulosa cells isolated from mice were used for mechanical studies. Results High miR-140 expression was observed in PCOS samples and insulin-treated granulosa cells compared to that in non-PCOS and unstimulated cells, respectively. However, the Ras-related protein Rap-2a precursor (RAP2A) was downregulated in in PCOS. MTT assay and EdU staining showed that an miR-140 inhibitor attenuated viability in insulin-treated granulosa cells; cell viability increased with miR-140 overexpression. Reduced expression of miR-140 and the expression of the miR-140 mimic resulted in marked cell apoptosis, as evidenced by the results of PI flow cytometry and Annexin V-FITC; miR-140 overexpression results in downregulated RAP2A expression, and the miR-140 mimic directly bound to the RAP2A 3′-UTR, causing increase in RAP2A levels in insulin-treated granulosa cells; RNA-mediated silencing of RAP2A in insulin-treated granulosa cells restored cell proliferation and apoptosis to normal levels. Phosphorylated AKT was found to be negatively regulated through cross-talk between miR-140 and RAP2A. Conclusions In conclusion, PCOS ovarian cortex specimens and insulin-treated granulosa cells showed elevated expression of miR-140, which could lead to increased proliferation and reduced apoptosis of cells by targeting RAP2A. This study may pave the way for future research on the properties of granulosa cells in PCOS. |
| first_indexed | 2024-04-09T22:42:11Z |
| format | Article |
| id | doaj.art-0173e64852b648b189faeb9a7db0a6bf |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-09T22:42:11Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-0173e64852b648b189faeb9a7db0a6bf2023-03-22T12:03:43ZengBMCJournal of Ovarian Research1757-22152020-02-0113111110.1186/s13048-020-0611-4RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cellsZhengfang Xiong0Bing Li1Wenjuan Wang2Xianghui Zeng3Binye Li4Shengyan Jian5Liyun Wang6Reproductive Medical Center, Qinghai Provincial People’s HospitalDepartment of General Surgery, Qinghai Provincial People’s HospitalReproductive Medical Center, Qinghai Provincial People’s HospitalReproductive Medical Center, Qinghai Provincial People’s HospitalReproductive Medical Center, Qinghai Provincial People’s HospitalReproductive Medical Center, Qinghai Provincial People’s HospitalReproductive Medical Center, Qinghai Provincial People’s HospitalAbstract Background We elucidated the role of specific MicroRNAs (miRNAs) in the development of polycystic ovary syndrome (PCOS) and explained the changes in the proliferation of granulosa cells. Excised ovarian cortex specimens were collected for miRNA profiling analysis (n = 20 PCOS females and 5 non-PCOS females). Insulin-treated ovarian granulosa cells isolated from mice were used for mechanical studies. Results High miR-140 expression was observed in PCOS samples and insulin-treated granulosa cells compared to that in non-PCOS and unstimulated cells, respectively. However, the Ras-related protein Rap-2a precursor (RAP2A) was downregulated in in PCOS. MTT assay and EdU staining showed that an miR-140 inhibitor attenuated viability in insulin-treated granulosa cells; cell viability increased with miR-140 overexpression. Reduced expression of miR-140 and the expression of the miR-140 mimic resulted in marked cell apoptosis, as evidenced by the results of PI flow cytometry and Annexin V-FITC; miR-140 overexpression results in downregulated RAP2A expression, and the miR-140 mimic directly bound to the RAP2A 3′-UTR, causing increase in RAP2A levels in insulin-treated granulosa cells; RNA-mediated silencing of RAP2A in insulin-treated granulosa cells restored cell proliferation and apoptosis to normal levels. Phosphorylated AKT was found to be negatively regulated through cross-talk between miR-140 and RAP2A. Conclusions In conclusion, PCOS ovarian cortex specimens and insulin-treated granulosa cells showed elevated expression of miR-140, which could lead to increased proliferation and reduced apoptosis of cells by targeting RAP2A. This study may pave the way for future research on the properties of granulosa cells in PCOS.https://doi.org/10.1186/s13048-020-0611-4Polycystic ovarian syndromeOvarian granulosa cellsmiR-140RAP2AAKT |
| spellingShingle | Zhengfang Xiong Bing Li Wenjuan Wang Xianghui Zeng Binye Li Shengyan Jian Liyun Wang RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells Journal of Ovarian Research Polycystic ovarian syndrome Ovarian granulosa cells miR-140 RAP2A AKT |
| title | RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells |
| title_full | RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells |
| title_fullStr | RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells |
| title_full_unstemmed | RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells |
| title_short | RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells |
| title_sort | retracted article mir 140 targets rap2a to enable the proliferation of insulin treated ovarian granulosa cells |
| topic | Polycystic ovarian syndrome Ovarian granulosa cells miR-140 RAP2A AKT |
| url | https://doi.org/10.1186/s13048-020-0611-4 |
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