Dataset Information

Restoration of miR-223-3p expression in aged mouse uteri with Samul-tang administration

ABSTRACT:

Background

During the secretory phase of the estrous cycle, endometrium senescence is accompanied by biological mechanisms such as metabolic dysfunction and epigenetic changes, leading to decreased embryo receptivity and implantation failure. Samul-tang has been reported to improve implantation potential in aged mice.

Methods

To uncover the age-related changes in the transcriptomes, we performed QuantSeq 3′mRNA sequencing to compare the mRNA expression patterns in the uteri between young and old mice. Young and old female BALB/c mice were administered distilled water or Samul-tang for 4 weeks, and the corresponding effects on the uteri of aged mice were investigated.

Results

We found 586 differentially expressed genes between the young and old mouse groups. Functional annotation analysis revealed 10 important pathways, including arachidonic acid metabolism and glutathione metabolism, involved in uterine cellular proliferation and decidualization. Using in silico analysis, we identified the three most abundantly interacting microRNAs―miR-223–3p, 155–5p, and 129–5p―with differentially expressed genes associated with important biological pathways. Samul-tang administration restored the expression of miR-223–3p, which could interact with important genes such as histamine ammonia-lyase (Hal) and acid phosphatase 5 (Acp5) for embryo implantation.

Conclusion

Our study demonstrated that uterine aging changes the expression of genes involved in metabolic pathways that are crucial to uterine health, leading to cellular senescence. We postulate that the regulation of miR-223–3p via Samul-tang administration can be of therapeutic importance in cellular senescence.

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PROVIDER: S-EPMC8814392 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundMicroRNAs have an important role in diverse biological processes including tumorigenesis. MiR-223 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in lung squamous cell carcinoma (LSCC). The following study investigates the role of miR-223-3p in LSCC growth and metastasis and its underlying mechanism.MethodsMicroRNA profiling analyses were conducted to determine differential miRNAs expression levels in LSCC tumor tissues that successfully formed xenografts in immunocompromised mice (XG) and failed tumor tissues (no-XG). RT-PCR and in situ hybridization (ISH) was performed to evaluate the expression of miR-223-3p in 12 paired adjacent normal tissues and LSCC specimens. Cell proliferation and migration were assessed by CCK-8, colony formation and Transwell assay, respectively. The role of miR-223-3p in LSCC tumorigenesis was examined using xenograft nude models. Bioinformatics analysis, Dual-luciferase reporter assays, Chromatin immunoprecipitation (ChIP) assay and Western blot analysis were used to identify the direct target of miR-223-3p and its interactions.ResultsMiR-223-3p was downregulated in LSCC tissues that successfully formed xenografts (XG) compared with tumor tissues that failed (no-XG), which was also significantly reduced in LSCC tissues compared with the adjacent normal tissues. Gain- and loss-of function experiments showed that miR-223-3p inhibited proliferation and migration in vitro. More importantly, miR-223-3p overexpression greatly suppressed tumor growth in vivo. Mechanistically, we found that mutant p53 bound to the promoter region of miR-223 and reduced its transcription. Meanwhile, p53 is a direct target of miR-223-3p. Thus, miR-223-3p regulated mutant p53 expression in a feedback loop that inhibited cell proliferation and migration.ConclusionsOur study identified miR-223-3p, as a tumor suppressor gene, markedly inhibited cell proliferation and migration via miR-223-3p-mutant p53 feedback loop, which suggested miR-223-3p might be a new therapeutic target in LSCC bearing p53 mutations.