MicroRNA-139-5p Regulates Fibrotic Potentials via Modulation of Collagen Type 1 and Phosphorylated p38 MAPK in Uterine Leiomyoma

Ahn, So Hyun; Kim, Heeyon; Lee, Inha; Lee, Jae Hoon; Cho, SiHyun; Choi, Young Sik

doi:10.3349/ymj.2021.62.8.726

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…Recently, there has been increasing evidence that miRNA can regulate more than 30% of the encoding genes in mammals and play a vital role in the pathogenesis and development of various human diseases, including UF ( Ali et al, 2020 ). For example, downregulated miR-139-5p contributed to the progression of UF through collagen Ⅰ deposition and p38 phosphorylation ( Ahn et al, 2021 ). The caspase-3 cleavage and elongation factor-2 phosphorylation were activated by miR-21, leading to UF cell apoptosis and stalled translation ( Fitzgerald et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of miRNA-TF-mRNA Regulatory Networks in Uterine Fibroids

Peng

Liu

et al. 2022

Front. Bioeng. Biotechnol.

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Uterine fibroids (UF) are the most common benign gynecologic tumors and lead to heavy menstrual bleeding, severe anemia, abdominal pain, and infertility, which seriously harm a women’s health. Unfortunately, the regulatory mechanisms of UF have not been elucidated. Recent studies have demonstrated that miRNAs play a vital role in the development of uterine fibroids. As a high-throughput technology, microarray is utilized to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between UF and myometrium. We identified 373 candidate DEGs and the top 100 DEMs. Function enrichment analysis showed that candidate DEGs were mainly enriched in biological adhesion, locomotion and cell migration, and collagen-containing extracellular matrix. Subsequently, protein-protein interaction (PPI) networks are constructed to analyze the functional interaction between DEGs and screen hub DEGs. Subsequently, the expression levels of hub DEGs were validated by real-time PCR of clinical UF samples. The DGIdb database was used to select candidate drugs for hub DEGs. Molecular docking was applied to test the affinity between proteins and drugs. Furthermore, target genes for 100 candidate DEMs were predicted by miRwalk3.0. After overlapping with 373 candidate DEGs, 28 differentially expressed target genes (DEGTs) were obtained. A miRNA-mRNA network was constructed to investigate the interactions between miRNA and mRNA. Additionally, two miRNAs (hsa-miR-381-3p and hsa-miR-181b-5p) were identified as hub DEMs and validated through RT-PCR. In order to better elucidate the pathogenesis of UF and the synergistic effect between miRNA and transcription factor (TF), we constructed a miRNA-TF-mRNA regulatory network. Meanwhile, in vitro results suggested that dysregulated hub DEMs were associated with the proliferation, migration, and apoptosis of UF cells. Our findings provided a novel horizon to reveal the internal mechanism and novel targets for the diagnosis and treatment of UF.

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Section: Introductionmentioning

confidence: 99%

Identification and Validation of miRNA-TF-mRNA Regulatory Networks in Uterine Fibroids

Peng

Liu

et al. 2022

Front. Bioeng. Biotechnol.

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“…The overexpression of each mir-29 family member reduced the ECM production in UF cells [ 91 , 92 , 93 , 94 ]. Another microRNA, miR-139-5p, regulated fibrotic potentials via the modulation of collagen type I and phosphorylated p38 MAPK in UFs [ 95 ]. The expression of miR-129 was also lower in UFs.…”

Section: Targeting Ecmmentioning

confidence: 99%

Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

Yang

Al-Hendy

2023

IJMS

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Uterine fibroids (UFs), also known as leiomyomas, are benign tumors of the myometrium affecting over 70% of women worldwide, particularly women of color. Although benign, UFs are associated with significant morbidity; they are the primary indication for hysterectomy and a major source of gynecologic and reproductive dysfunction, ranging from menorrhagia and pelvic pain to infertility, recurrent miscarriage, and preterm labor. So far, the molecular mechanisms underlying the pathogenesis of UFs are still quite limited. A knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve UF patient outcomes. Excessive ECM accumulation and aberrant remodeling are crucial for fibrotic diseases and excessive ECM deposition is the central characteristics of UFs. This review summarizes the recent progress of ascertaining the biological functions and regulatory mechanisms in UFs, from the perspective of factors regulating ECM production, ECM-mediated signaling, and pharmacological drugs targeting ECM accumulation. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor.

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“…Another member of the miRNA known as the miR-200 with the p38 have been associated with significant role of reactive oxygen species production which are linked to the development of liver cancer by promoting apoptosis [7]. Recently, it was discovered that another family of the miRNA known as the miR-139-5p, plays important roles in the regulation cell to cell migration and its expression has been associated with the phosphorylation of the MAPK/p38 leading to the uncontrolled movement of cells [31].…”

Section: Micro Rna Regulates the Activation Of Mapk/p38mentioning

confidence: 99%

The Role of MAPK/p38 Signalling Pathway in Cancer

Behjat

2023

J Clin Med Res.

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Cancer is one of the fatal diseases globally. It is unfortunate that despite many years of devoted studies towards finding a better therapeutic approach, the scourge of the disease has continued to rise with attendant mortalities. Many studies have been devoted to finding constructive clues to the pathways that are implicated in the onset and progression of cancer. Recently, increasing bodies of studies have identified the MAPK/p38 role in its pathological pathways. The current review effort explored different functions of MAPK/p38 in the onset and progression of cancer. This signaling pathway is crucial for the overall integrity of the cell and its regulation has been associated with tumorigenesis and cancer metastasis. Several scientific research have also identified its roles in the ability of cancer cells to resist chemotherapeutic interventions. However, to fully explore the MAPK, studies that will elucidate the various MAPK/p38 isoforms and their roles in tumorigenesis may proffer the next revolution in the fight against cancer incidences.

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MicroRNA-139-5p Regulates Fibrotic Potentials via Modulation of Collagen Type 1 and Phosphorylated p38 MAPK in Uterine Leiomyoma

Cited by 6 publications

References 40 publications

Identification and Validation of miRNA-TF-mRNA Regulatory Networks in Uterine Fibroids

Identification and Validation of miRNA-TF-mRNA Regulatory Networks in Uterine Fibroids

Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids

The Role of MAPK/p38 Signalling Pathway in Cancer

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