Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients
BackgroundSchizophrenia (SCZ) is a serious chronic mental disorder. Our previous case–control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship betwee...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1187111/full |
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| author | Qian Peng Zhun Dai Jingwen Yin Dong Lv Xudong Luo Susu Xiong Zhijiang Yang Guangmin Chen Yaxue Wei Ying Wang Dandan Zhang Lulu Wang Debo Yu Yusheng Zhao Dele Lin Zhiyu Liao Yongxi Zhong Zhixiong Lin Juda Lin |
| author_facet | Qian Peng Zhun Dai Jingwen Yin Dong Lv Xudong Luo Susu Xiong Zhijiang Yang Guangmin Chen Yaxue Wei Ying Wang Dandan Zhang Lulu Wang Debo Yu Yusheng Zhao Dele Lin Zhiyu Liao Yongxi Zhong Zhixiong Lin Juda Lin |
| author_sort | Qian Peng |
| collection | DOAJ |
| description | BackgroundSchizophrenia (SCZ) is a serious chronic mental disorder. Our previous case–control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study.MethodsGenotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR.ResultsBased on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137.ConclusionThe plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future. |
| first_indexed | 2024-03-12T13:40:43Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-03-12T13:40:43Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-f03e585afef44a14aadccba01ef4316d2023-08-23T19:28:51ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402023-08-011410.3389/fpsyt.2023.11871111187111Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patientsQian PengZhun DaiJingwen YinDong LvXudong LuoSusu XiongZhijiang YangGuangmin ChenYaxue WeiYing WangDandan ZhangLulu WangDebo YuYusheng ZhaoDele LinZhiyu LiaoYongxi ZhongZhixiong LinJuda LinBackgroundSchizophrenia (SCZ) is a serious chronic mental disorder. Our previous case–control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study.MethodsGenotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR.ResultsBased on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137.ConclusionThe plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1187111/fullschizophreniaestrogenmiR-137single nucleotide polymorphismsgenetic associationgene expression in vitro |
| spellingShingle | Qian Peng Zhun Dai Jingwen Yin Dong Lv Xudong Luo Susu Xiong Zhijiang Yang Guangmin Chen Yaxue Wei Ying Wang Dandan Zhang Lulu Wang Debo Yu Yusheng Zhao Dele Lin Zhiyu Liao Yongxi Zhong Zhixiong Lin Juda Lin Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients Frontiers in Psychiatry schizophrenia estrogen miR-137 single nucleotide polymorphisms genetic association gene expression in vitro |
| title | Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients |
| title_full | Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients |
| title_fullStr | Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients |
| title_full_unstemmed | Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients |
| title_short | Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients |
| title_sort | schizophrenia plausible protective effect of microrna 137 is potentially related to estrogen and prolactin in female patients |
| topic | schizophrenia estrogen miR-137 single nucleotide polymorphisms genetic association gene expression in vitro |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1187111/full |
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