MiR-18a-5p contributes to enhanced proliferation and migration of PASMCs via targeting Notch2 in pulmonary arterial hypertension

Miao, Renying; Liu, Wanli; Qi, Chaoran; Song, Yan; Yong-gan, Zhang; Fu, Yiqun; Liu, Weiping; Lang, Yuchang; Zhang, Yifei; Zhang, Zhimin

doi:10.1016/j.lfs.2020.117919

Cited by 15 publications

(8 citation statements)

References 33 publications

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“…However, given the small number of researches directly focused on the association between miR-18a and HCC, we tried to obtain a rough estimate of the possible target gene-depend functions of miR-18a through investigating published studies in PubMed database. As expected, several target genes predicted in our analysis involving SOX6, NOTCH2, RORA, NEDD9 [33,[37][38][39], etc, have been validated to mediate the effects of miR-18a in multiple types of cell lines and tissues mainly through promoting proliferation and migration. Notably, in the study of Zheng et.…”

Section: Discussionsupporting

confidence: 71%

Potential prognostic value of hsa-miR-18a in hepatocellular carcinoma and the underlying key down-stream gene CHRM2: a comprehensive bioinformatic analysis*

Wen

Wei

et al. 2021

Preprint

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Background Hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related death. Better prognosticators are warranted for HCC. Hsa-miR-18a has been considered implicated in the pathogenesis of several tumors including HCC. Methods Bioinformatic analyses were conducted to predict target genes and carry out enrichment analysis. Validated downstream genes of hsa-miR-18a were obtained from PubMed database. Differential expression analysis was conducted within the “edgeR” R package based on the TCGA datasets. Survival analysis was performed by Kaplan-Meier survival analysis. All the visualizations were implemented by R. Results Bioinformatic analysis obtained a total of 90 target genes of hsa-miR-18a and revealed that target genes were involved in pathways essential for cancer onset and development such as cell cycle and PI3K/AKT signaling pathway. A review of literatures found target genes of miR-18a indeed participating in the biological processes of HCC. CHRM2 was identified as a special gene after the intersection analysis of TCGA differentially expressed genes (DEGs) and predicted target genes. Survival analysis validated that hsa-miR-18a and CHRM2 significantly affected the prognosis of HCC patients. Conclusion There is a strong association between hsa-miR-18a with tumors including HCC via participating essential tumor-promoting pathways including cell cycle, PI3K/AKT signaling pathway, etc. Furthermore, high miR-18a expression and low CHRM2 expression could lead to a poor prognosis in HCC. In conclusion, miR-18a could serve as an expectational prognostic biomarker in HCC.

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Section: Discussionsupporting

confidence: 71%

Potential prognostic value of hsa-miR-18a in hepatocellular carcinoma and the underlying key down-stream gene CHRM2: a comprehensive bioinformatic analysis*

Wen

Wei

et al. 2021

Preprint

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“…In PAH patients, PASMC function is also tightly controlled by upregulated miR-18a-5p, through targeting of Notch2. While in PAH patients, miR-18a-5p influences PASMC proliferation and migration [184]. In MCT-treated rat PASMCs metabolism is affected by miR-125a-5p, through targeting of hexokinase 2 (HK2) and subsequent decrease in glycolysis [185].…”

Section: Non-coding Rnas Involved In Pahmentioning

confidence: 99%

Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?

Kocken

Martins

2020

IJMS

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Pulmonary artery hypertension (PAH) is a rare chronic disease with high impact on patients’ quality of life and currently no available cure. PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). This remodeling eventually leads to increased pressure in the right ventricle (RV) and subsequent right ventricle hypertrophy (RVH) which, when left untreated, progresses into right ventricle failure (RVF). PAH can not only originate from heritable mutations, but also develop as a consequence of congenital heart disease, exposure to drugs or toxins, HIV, connective tissue disease or be idiopathic. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the epigenetic mechanisms driving the disease occurred. In this review, we reflect on the different epigenetic regulatory factors that are associated with the pathology of RV remodeling, and on their relevance towards a better understanding of the disease and subsequently, the development of new and more efficient therapeutic strategies.

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“…Recently, a series of studies demonstrated that hypoxic modulation of cellular function could be mediated by miRNAs during the development of cancer (36)(37)(38). HPH and cancer have similar phenotypes because both diseases are characterized by increased cell proliferation and migration (39,40). The present study chose miR-153 as the research target because previous studies have reported its antitumor function in different types of cancer including papillary thyroid and breast cancer (41,42).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑153 attenuates hypoxia‑induced excessive proliferation and migration of pulmonary arterial smooth muscle cells by targeting ROCK1 and NFATc3

Zhao

Wang

et al. 2021

Mol Med Rep

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The aim of the present study was to explore the effect of microRNA (miR)-153 on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in a hypoxic condition by targeting ρ-associated, coiled-coil-containing protein kinase 1 (ROCK1) and nuclear factor of activated T cells cytoplasmic 3 (NFATc3). The right ventricular systolic pressure, right ventricular hypertrophy index, medial wall thickness and medial wall area were studied at different time-points after rats were exposed to hypoxia. Western blot analysis was used to detect ROCK1 and NFATc3 protein levels. In addition, reverse transcription-quantitative (RT-q) PCR was performed to confirm the mRNA levels of miR-153, ROCK1 and NFATc3 in human (H)PASMCs under hypoxic conditions. Transfected cells were then used to evaluate the effect of miR-153 on cell proliferation and migration abilities. The association between miR-153 and ROCK1 or NFATc3 was identified through double luciferase assays. Hypoxia induced pulmonary vascular remodeling and pulmonary arterial hypertension, which resulted from the abnormal proliferation of HPASMCs. ROCK1 and NFATc3 were the target genes of miR-153 and miR-153 mimic inhibited the protein expressions of ROCK1 and NFATc3 in HPASMCs and further inhibited cell proliferation and migration under hypoxic conditions. By contrast, the miR-153 inhibitor promoted the proliferation and migration of HPASMCs. miR-153 regulated the proliferation and migration of HPASMCs under hypoxia by targeting ROCK1 and NFATc3.

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MiR-18a-5p contributes to enhanced proliferation and migration of PASMCs via targeting Notch2 in pulmonary arterial hypertension

Cited by 15 publications

References 33 publications

Potential prognostic value of hsa-miR-18a in hepatocellular carcinoma and the underlying key down-stream gene CHRM2: a comprehensive bioinformatic analysis*

Potential prognostic value of hsa-miR-18a in hepatocellular carcinoma and the underlying key down-stream gene CHRM2: a comprehensive bioinformatic analysis*

Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?

MicroRNA‑153 attenuates hypoxia‑induced excessive proliferation and migration of pulmonary arterial smooth muscle cells by targeting ROCK1 and NFATc3

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