Fan Weisen, Zhang Yingjie, Wang Dandan, Wang Chen, Yang Jie
The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250013, China.
School of Health, Shandong University of Traditional Chinese Medicine, Jinan, 250013, China.
Heliyon. 2023 Sep 9;9(9):e20022. doi: 10.1016/j.heliyon.2023.e20022. eCollection 2023 Sep.
Premature ovarian insufficiency（POI）is a female reproductive aging illness. Yiwei decoction（YWD） is a traditional treatment for Yangming nourishment. YWD can treat premature ovarian insufficiency, but the exact molecular mechanism is unknown. As a result, the differential expression of Long noncoding RNAs (LncRNAs) and Circular RNAs(CircRNAs) in the ovary of POI rats after YWD treatment was investigated in this paper, and the CeRNA regulatory network was built. The model was created using cyclophosphamide. The model group + YWD was in Group A, the model control group was in Group B, and the regular control group was in Group C. In this study, 177 differential expression Long noncoding RNAs(DELncRNAs) and 190 differential expression Circular RNAs (DECircRNAs) were discovered between A and B (P＜0.05,|LogFC|＞1). Following the analysis, 27 DELncRNAs and 96 DECircRNAs (P-adjusted＜0.05,|LogFC|＞1) were discovered. At the same time, we built the CeRNA network using differentially expressed mRNAs and microRNAs (miRNAs) expression between groups A and B. The DELncRNAs were used to construct a lncRNA-miRNA-mRNA ceRNA network with 27 LncRNAs, 4 miRNAs, and 19 mRNAs. The DECircRNAs were utilized to establish a CircRNA-miRNA-mRNA ceRNA network that was made up of 15 CircRNAs, 4 miRNAs, and 20 mRNA. The highly correlated regulatory networks were the LncMSTRG.22691.3/miR-3102/ANGPT4 and Circ10_34698898_34699378/miR-33-5p/TTC22. Circ20_12035276_12036793、Circ20_30693935_30696337、Circ4_157723097_157723378 and Circ4_157923266_157923904 occurred concurrently in AvsB, BvsC, and AvsC. MiRDB predicted eight target miRNAs for these CircRNAs. The miRanda(score = 140，energy = -1) binding energy calculation revealed that seven miRNAs were well combined with three CircRNA base complementary pairs. This implies that 3 DECircRNAs could serve as spongy bodies for these miRNAs. Network pharmacological analysis showed that ten active components in YWD may regulate the expression of LncRNAs and CircRNAs, such as Stigmasterol, Uridine, Ophiopogonanone A, Gamma-Aminobutyric Acid, and others. In conclusion, this study combined transcriptomics and network pharmacological analysis to identify differentially expressed lncRNAs as well as CircRNAs in ovaries of YWD-treated POI rats, thereby constructing ceRNA networks implicated in POI. This would contribute to clarifying the pathways by which Chinese herbal compounds regulate gene expression in POI.
卵巢早衰（POI）是一种女性生殖衰老疾病。益胃汤（YWD）是一种传统的阳明滋养疗法。YWD可以治疗卵巢早衰，但其确切的分子机制尚不清楚。因此，本文研究了YWD治疗后POI大鼠卵巢中长链非编码RNA（LncRNAs）和环状RNA（CircRNAs）的差异表达，并构建了竞争性内源RNA（CeRNA）调控网络。该模型采用环磷酰胺建立。模型组+YWD为A组，模型对照组为B组，正常对照组为C组。本研究发现，A组和B组之间有177个差异表达的长链非编码RNA（DELncRNAs）和190个差异表达的环状RNA（DECircRNAs）（P＜0.05，|LogFC|＞1）。经过分析，发现了27个DELncRNAs和96个DECircRNAs（P调整后＜0.05，|LogFC|＞1）。同时，利用A组和B组之间差异表达的信使核糖核酸（mRNAs）和微小核糖核酸（miRNAs）构建了CeRNA网络。DELncRNAs用于构建一个由27个LncRNAs、4个miRNAs和19个mRNAs组成的lncRNA-miRNA-mRNA ceRNA网络。DECircRNAs用于建立一个由15个CircRNAs、4个miRNAs和20个mRNA组成的CircRNA-miRNA-mRNA ceRNA网络。高度相关的调控网络是LncMSTRG.22691.3/miR-3102/ANGPT4和Circ10_34698898_34699378/miR-33-5p/TTC22。Circ20_12035276_12036793、Circ20_30693935_30696337、Circ4_157723097_157723378和Circ4_157923266_157923904在A组与B组、B组与C组以及A组与C组中同时出现。MiRDB预测这些CircRNAs有8个靶标miRNAs。miRanda（得分=140，能量=-1）结合能计算表明，7个miRNAs与3个CircRNA碱基互补对结合良好。这意味着3个DECircRNAs可以作为这些miRNAs的海绵体。网络药理学分析表明，YWD中的10种活性成分可能调节LncRNAs和CircRNAs的表达，如豆甾醇、尿苷、麦冬黄酮A、γ-氨基丁酸等。总之，本研究结合转录组学和网络药理学分析，鉴定了YWD治疗的POI大鼠卵巢中差异表达的lncRNAs和CircRNAs，从而构建了与POI相关的CeRNA网络。这将有助于阐明中药化合物调节POI中基因表达的途径。
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