Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α)

Bai, Bing; Liu, Ying; Fu, Xuemei; Qin, Haiyan; Li, Gao-Kai; Wang, Hai-Chen; Sun, Shilong

doi:10.1155/2022/7608712

Cited by 13 publications

(10 citation statements)

References 40 publications

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“…MiR‐138‐5p was characterized as a tumor suppressor in bladder cancer, 16 , 17 colorectal cancer, 18 breast cancer, 19 and hepatocellular carcinoma. 20 , 21 To determine the diagnostic value of miR‐138‐5p as a biomarker of lung cancer, we investigated miR‐138‐5p expression in 18 lung cancer serum samples and matched adjacent normal serum samples through qRT‐PCR. The miR‐138‐5p expression was significantly reduced in the lung cancer serum samples compared with normal controls ( p < 0.001) (Figure 1a ).…”

Section: Resultsmentioning

confidence: 99%

MiR‐138‐5p suppresses the progression of lung cancer by targeting SNIP1

Han

Yang

et al. 2023

Thoracic Cancer

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Background MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR‐138‐5p in lung cancer progression and the value of miR‐138‐5p in lung cancer diagnosis. Methods Quantitative real‐time PCR was performed to examine the expressions of miR‐138‐5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR‐138‐5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR‐138‐5p on cell proliferation and metastasis by CCK‐8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay. Results MiR‐138‐5p was decreased in the serum of patients with non‐small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR‐138‐5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR‐138‐5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR‐138‐5p directly binds to the 3′‐untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c‐Myc. Moreover, overexpression of SNIP1 rescues the miR‐138‐5p‐mediated inhibition in NSCLC cells. Conclusions The results suggested that miR‐138‐5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR‐138‐5p is a novel and valuable biomarker for NSCLC diagnosis.

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Section: Resultsmentioning

confidence: 99%

MiR‐138‐5p suppresses the progression of lung cancer by targeting SNIP1

Han

Yang

et al. 2023

Thoracic Cancer

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“…The overexpression of miR-138-5 significantly suppresses the expression level of HIF-1α ( Bai et al, 2022 ). Additionally, it has been demonstrated the protective effect of miR-138-5 on cardiovascular damage due to the inhibition of aldosterone synthase (CYP11B2) leading to reversal of cardiac fibrotic remodeling ( Kim et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of oral stem cells extracellular vesicles on cardiomyocytes in hypoxia-reperfusion

Della Rocca,

Diomede,

Konstantinidou

et al. 2024

Front. Cell Dev. Biol.

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Hypoxia signaling plays an important role in physiological and pathological conditions. Hypoxia in the heart tissue can produce different consequences depending on the duration of exposure to the hypoxic state. While acute hypoxic exposure leads to a reversible acclimatization in heart tissue with normal systemic oxygen supply, chronic hypoxia exacerbates cardiac dysfunction, leads to a destruction of the tissue. Extracellular vesicles (EVs) are small membrane vesicles that act as mediators of intercellular communication. EVs are secreted by different cell types and those produced by oral cavity-derived mesenchymal stem cells (MSCs), including human gingival MSCs (hGMSCs), have pro-angiogenic and anti-inflammatory effects and showed therapeutic role in tissue regeneration. The aim of the present work was to evaluate the potential protective and regenerative role of EVs produced by hGMSCs, in an in vitro model of hypoxia-conditioned HL-1 cardiomyocytes through the expression analysis of following inflammatory, oxidative stress, angiogenesis, cell survival and apoptotic markers: HIF-1α, P300, NFkB, CCL2, IL1B, IL6, NRF2, CASP-3, BAX and VEGF. Results showed that hGMSCs-derived EVs exerted protection HL-1 cardiomyocytes exposed to both pre and post hypoxic conditions. Moreover, modulation of CASP3 and BAX expression demonstrated that EVs reduced the apoptosis. The analysis of microRNAs in EVs derived from hGMSCs was performed to assess the epigenetic regulation of the presented markers. The following microRNAs: hsa-miR-138-5p, hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-21-5p, hsa-miR-324-5p, hsa-miR-133a-3p, hsa-miR-150-5p, hsa-miR-199a-5p, hsa-miR-128-3p and hsa-miR-221-3p can directly or indirectly target the studied genes by determining their modulation obtained in our study. The data from this study suggested that EVs obtained from hGMSCs may be considered for the cell free treatment option in hypoxia-driven cardiac tissue dysfunction.

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“…Therefore, the mRNA risk signature we constructed has an essential effect on the prognosis and development of HCC. Previous studies have shown that seven mRNAs in the mRNA risk signature can act as oncogenes to promote HCC progression, including PPM1G [ 39 ], PHOSPHO2 [ 40 ], YBX1 [ 41 ], PSRC1 [ 42 ], UCK2 [ 43 ], EZH2 [ 44 ], and CDCA8 [ 45 ]. However, MEX3A, TAF3, TMEM69, and DYNC1LI1 have not been experimentally studied in HCC.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and Associated mRNA Risk Signature in Hepatocellular Carcinoma

Wang,

Hu,

Nie

et al. 2023

Analytical Cellular Pathology

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Currently, 80%–90% of liver cancers are hepatocellular carcinomas (HCC). HCC patients develop insidiously and have an inferior prognosis. The methyltransferase-like (METTL) family principal members are strongly associated with epigenetic and tumor progression. The present study mainly analyzed the value of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and associated mRNA risk signature for HCC. METTLs expression is upregulated in HCC and is a poor prognostic factor in HCC. METTLs were upregulated in patients older than 60 and associated with grade. Except for METTL25, the remaining 10 genes were associated with the HCC stage, invasion depth (T). In addition, METTLs showed an overall alteration rate of 50%. Except for METTL13/2A/25/9, the expression of the other seven genes was significantly associated with overall survival, disease-specific survival, and progression-free survival. Multivariate studies have shown that METTL21A/6 can be an independent prognostic marker in HCC. A total of 664 mRNAs were selected based on Pearson correlation coefficient (R > 0.5), unsupervised consensus clustering, weighted coexpression network analysis, and univariate Cox analysis. These mRNAs were significantly associated with METTLs and were poor prognostic factors in HCC patients. The least absolute shrinkage and selection operator (lasso) was used to construct the best METTLs associated with mRNA risk signature. The mRNA risk signature was significantly associated with age, stage, and t grade. The mRNA high-risk group had higher TP53 and RB1 mutations. This study constructed a nomogram with the mRNA risk profile and clinicopathological features, which could better predict the OS of individuals with HCC. We also analyzed associations between METTLs and mRNA risk signatures in epithelial-mesenchymal transition, immune checkpoints, immune cell infiltration, tumor mutational burden, microsatellite instability, cancer stem cells, tumor pathways, and drug sensitivity. In addition, this study constructed a protein interaction network network including METTLs and mRNA risk signature genes related to tumor microenvironment remodeling based on single-cell sequencing. In conclusion, this study provides a theoretical basis for the mechanism, biomarker screening, and treatment of HCC.

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Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α)

Cited by 13 publications

References 40 publications

MiR‐138‐5p suppresses the progression of lung cancer by targeting SNIP1

MiR‐138‐5p suppresses the progression of lung cancer by targeting SNIP1

Protective effect of oral stem cells extracellular vesicles on cardiomyocytes in hypoxia-reperfusion

Comprehensive Analysis of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and Associated mRNA Risk Signature in Hepatocellular Carcinoma

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