MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5

Tong, Jie; Zhang, Min; Li, Xia; Ren, Guohai

doi:10.3892/mmr.2020.11775

Cited by 11 publications

(3 citation statements)

References 35 publications

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“…PRDX1 (peroxiredoxin 1) is a known modulator of reactive oxygen species that regulates oxidative stress and BMP signalling-driven osteogenesis [ 35 ]. OXSM (mitochondrial 3-oxoacyl-ACP synthase) reportedly targets miR338-3p [ 36 ], which has important functions in regulating bone homeostasis in OP [ 37 ]. The present study confirmed that these genes—SLC7A11, RAC1, PRDX1 and OXSM—encoding disulfidptosis activators exhibited higher expression levels in OP samples, thereby activating disulfidptosis processes in OP.…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis

Zhang,

Li,

Chen

et al. 2024

Aging

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Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.

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Section: Discussionmentioning

confidence: 99%

RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis

Zhang,

Li,

Chen

et al. 2024

Aging

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“…MiR‐338‐3p is a miRNA that is shown to be involved in the prevention of osteoporosis by targeting a variety of signal molecules and signaling pathways, such as proprotein convertase subtilisin/kexin type 5 (PCSK5), Runx2, Fgfr2, and RANKL (Liu et al, 2014; Tong et al, 2021; Zhang et al, 2016). A study has indicated that RSV reduces the expression of miR‐338‐3p in ovariectomized rats.…”

Section: Resveratrolmentioning

confidence: 99%

Therapeutic effects of resveratrol on epigenetic mechanisms in age‐related diseases: A comprehensive review

Zhang,

Kiarasi

2024

Phytotherapy Research

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Recently, various studies have shown that epigenetic changes are associated with aging and age‐related diseases. Both animal and human models have revealed that epigenetic processes are involved in aging mechanisms. These processes happen at multiple levels and include histone modification, DNA methylation, and changes in noncoding RNA expression. Consequently, changes in the organization of chromatin and DNA accessibility lead to the regulation of gene expression. With increasing awareness of the pivotal function of epigenetics in the aging process, researchers' attention has been drawn to how these epigenetic changes can be modified to prevent, stop, or reverse aging, senescence, and age‐related diseases. Among various agents that can affect epigenetic, polyphenols are well‐known phytochemicals found in fruits, vegetables, and plants. Polyphenols are found to modify epigenetic‐related mechanisms in various diseases and conditions, such as metabolic disorders, obesity, neurodegenerative diseases, cancer, and cardiovascular diseases. Resveratrol (RSV) is a member of the stilbene subgroup of polyphenols which is derived from various plants, such as grapes, apples, and blueberries. Therefore, herein, we aim to summarize how RSV affects different epigenetic processes to change aging‐related mechanisms. Furthermore, we discuss its roles in age‐related diseases, such as Alzheimer's, Parkinson's, osteoporosis, and cardiovascular diseases.

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“…Several studies reveal the involvement of microRNAs (miR-181a, miR-434-3p, miR-431, miR-29, and miR-126) in the skeletal muscle aging process [10][11][12]. The group of miRNAs such as microRNA-19b-3p (Liu et al, 2022) [13], miRNA-365a-3p [14], miRNA-577 [15], and miRNA-338-3p [16] is involved in the age-related bone loss.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting MicroRNA-141-3p Improves Musculoskeletal Health in Aged Mice

et al. 2023

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Emerging evidence shows that the microRNA-141-3p is involved in various age-related pathologies. Previously, our group and others reported elevated levels of miR-141-3p in several tissues and organs with age. Here, we inhibited the expression of miR-141-3p using antagomir (Anti-miR-141-3p) in aged mice and explored its role in healthy aging. We analyzed serum (cytokine profiling), spleen (immune profiling), and overall musculoskeletal phenotype. We found decreased levels of pro-inflammatory cytokines (such as TNF-, IL-1, IFN-) in serum with Anti-miR-141-3p treatment. The flow-cytometry analysis on splenocytes revealed decreased M1 (pro-inflammatory) and increased M2 (anti-inflammatory) populations. We also found improved bone microstructure and muscle fiber size with Anti-miR-141-3p treatment. Molecular analysis revealed that miR-141-3p regulates the expression of AU-rich RNA-binding factor 1 (AUF1) and promotes senescence (p21, p16) and pro-inflammatory (TNF-, IL-1, IFN-) environment whereas inhibiting miR-141-3p prevents these effects. Furthermore, we demonstrated that the expression of FOXO-1 transcription factor was reduced with Anti-miR-141-3p and elevated with silencing of AUF1 (siRNA-AUF1), suggesting crosstalk between miR-141-3p and FOXO-1. Overall, our proof-of-concept study demonstrates that inhibiting miR-141-3p could be a potential strategy to improve immune, bone, and muscle health with age.

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MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5

Cited by 11 publications

References 35 publications

RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis

RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis

Therapeutic effects of resveratrol on epigenetic mechanisms in age‐related diseases: A comprehensive review

Inhibiting MicroRNA-141-3p Improves Musculoskeletal Health in Aged Mice

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