MicroRNAs target the Wnt/β‑catenin signaling pathway to regulate epithelial‑mesenchymal transition in cancer (Review)

Lei, Yuhe; Chen, Lei; Zhang, Ge; Shan, Aiyun; Ye, Chunfeng; Liang, Bin; Sun, Jiayu; Liao, Xin; Zhu, Changfeng; Chen, Yueyue; Wang, Jing; Zhang, Enxin; Deng, Lijuan

doi:10.3892/or.2020.7703

Cited by 36 publications

(33 citation statements)

References 195 publications

(199 reference statements)

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“…Restoration of miR-122 expression in HCC results in suppression of tumor growth and metastasis, and enhances chemosensitivity, suggesting that miR-122 functions as a tumor suppressor against HCC [ 47 ]. To date, several target genes of miR-122, such as cyclin G1, a disintegrin, and metalloprotease 10 (ADAM10), Wnt family member 1, Snail1/2, and pyruvate kinase M2, were identified to modulate hepatocarcinogenesis, the EMT, angiogenesis, and metabolism of HCC [ 47 , 48 , 49 , 50 , 51 ]. Our results indicated that G9a represents a novel, important target gene of miR-122 in regulating HCC progression.…”

Section: Discussionmentioning

confidence: 99%

Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122

Yuan

Lee

Yang

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers, which is the second most lethal tumor worldwide. Epigenetic deregulation is a common trait observed in HCC. Recently, increasing evidence suggested that the G9a histone methyltransferase might be a novel regulator of HCC development. However, several HCC cell lines were recently noted to have HeLa cell contamination or to have been derived from non-hepatocellular origin, suggesting that functional validation of G9a in proper HCC models is still required. Herein, we first confirmed that higher G9a messenger RNA and protein expression levels were correlated with poor overall survival (OS) and disease-free survival (DFS) rates of HCC patients from The Cancer Genome Atlas (TCGA) dataset and our recruited HCC cohort. In an in vitro functional evaluation of HCC cells, HCC36 (hepatitis B virus-positive (HBV+) and Mahlavu (HBV−)) cells showed that G9a participated in promoting cell proliferation, colony formation, and migration/invasion abilities. Moreover, orthotopic inoculation of G9a-depleted Mahlavu cells in NOD-SCID mice also resulted in a significantly decreased tumor burden compared to the control group. Furthermore, after surveying microRNA (miRNA; miR) prediction databases, we identified the liver-specific miR-122 as a G9a-targeting miRNA. In various HCC cell lines, we observed that miR-122 expression levels tended to be inversely correlated to G9a expression levels. In clinical HCC specimens, a significant inverse correlation of miR-122 and G9a mRNA expression levels was also observed. Functionally, the colony formation and invasive ability were attenuated in miR-122-overexpressing HCC cells. HCC patients with low miR-122 and high G9a expression levels had the worst OS and DFS rates compared to others. Together, our results confirmed the importance of altered G9a expression during HCC progression and discovered that a novel liver-specific miR-122-G9a regulatory axis exists.

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Section: Discussionmentioning

confidence: 99%

Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122

Yuan

Lee

Yang

et al. 2021

Cancers

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“…It is well known that Wnt signaling/β-catenin pathway dysregulation is involved in cancer genesis, including oral cancer. This pathway is accompanied by various mechanisms, such as epithelial-mesenchymal transition and involvement of various miRNAs [ 51 , 52 ]. Participation of miR-30c-5p targets in this signaling pathway as shown by the pathway enrichment analysis underlies its role in oral cancer development.…”

Section: Discussionmentioning

confidence: 99%

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma

Mehterov

Vladimirov

Sacconi³

et al. 2021

Biomedicines

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The levels of different classes of extracellular RNAs (exRNAs) remain stable in bodily fluids. The detection of either enriched or depleted specific subsets of salivary microRNAs (miRNAs) has the potential to serve as a non-invasive approach for biomarker development. Thus, salivary miRNAs have emerged as a promising molecular tool for early diagnosis and screening of oral squamous cell carcinoma (OSCC). Total RNA was extracted from saliva supernatant of 33 OSCC patients and 12 controls (discovery set), and the differential expression of 8 cancer-related miRNAs was detected by TaqMan assay. Among the screened miRNAs, miR-30c-5p (p < 0.04) was significantly decreased in OSCC saliva. The same transcriptional behavior of miR30c-5p was observed in an additional validation set. miR-30c-5p showed a significant statistical difference between cases and controls with areas under the curve (AUC) of 0.82 (95% CI: 0.71–0.89). The sensitivity and the specificity of miR-30c-5p were 86% and 74%, respectively. The target identification analysis revealed enrichment of miR-30c-5p targets in p53 and Wnt signaling pathways in OSCC. Additionally, the miR-30c-5p targets had clinical significance related to overall survival. In conclusion, these findings show that downregulated miR-30c-5p has the potential to serve as a novel, non-invasive biomarker for early OSCC detection.

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“…Moreover, several important pathways such as Wnt, mTOR, MAPK signaling, and miRNA in cancer were significantly enriched in KEGG pathway enrichment analysis (71)(72)(73)(74)(75). Recent reports suggest that Wnt signaling pathway regulates several crucial events, including EMT, cell migration, cell proliferation, and polarity of cells (76)(77)(78)(79)(80)(81). The association of Wnt signaling pathway and dysregulation of miRNA has been linked together in various cancer types.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer

et al. 2021

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BackgroundEpithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies among women worldwide. Early diagnosis of EOC could help in ovarian cancer management. MicroRNAs, a class of small non-coding RNA molecules, are known to be involved in post-transcriptional regulation of ~60% of human genes. Aberrantly expressed miRNAs associated with disease progression are confined in lipid or lipoprotein and secreted as extracellular miRNA in body fluid such as plasma, serum, and urine. MiRNAs are stably present in the circulation and recently have gained an importance to serve as a minimally invasive biomarker for early detection of epithelial ovarian cancer.MethodsGenome-wide methylation pattern of six EOC and two normal ovarian tissue samples revealed differential methylation regions of miRNA gene promoter through MeDIP-NGS sequencing. Based on log2FC and p-value, three hypomethylated miRNAs (miR-205, miR-200c, and miR-141) known to have a potential role in ovarian cancer progression were selected for expression analysis through qRT-PCR. The expression of selected miRNAs was analyzed in 115 tissue (85 EOC, 30 normal) and 65 matched serum (51 EOC and 14 normal) samples.ResultsAll three miRNAs (miR-205, miR-200c, and miR-141) showed significantly higher expression in both tissue and serum cohorts when compared with normal controls (p < 0.0001). The receiver operating characteristic curve analysis of miR-205, miR-200c, and miR-141 has area under the curve (AUC) values of 87.6 (p < 0.0001), 78.2 (p < 0.0001), and 86.0 (p < 0.0001), respectively; in advance-stage serum samples, however, ROC has AUC values of 88.1 (p < 0.0001), 78.9 (p < 0.0001), and 86.7 (p < 0.0001), respectively, in early-stage serum samples. The combined diagnostic potential of the three miRNAs in advance-stage serum samples and early-stage serum samples has AUC values of 95.9 (95% CI: 0.925–1.012; sensitivity = 96.6% and specificity = 80.0%) and 98.1 (95% CI: 0.941–1.021; sensitivity = 90.5% and specificity = 100%), respectively.ConclusionOur data correlate the epigenetic deregulation of the miRNA genes with their expression. In addition, the miRNA panel (miR-205 + miR-200c + miR-141) has a much higher AUC, sensitivity, and specificity to predict EOC at an early stage in both tissue and serum samples.

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MicroRNAs target the Wnt/β‑catenin signaling pathway to regulate epithelial‑mesenchymal transition in cancer (Review)

Cited by 36 publications

References 195 publications

Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122

Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122

Salivary miR-30c-5p as Potential Biomarker for Detection of Oral Squamous Cell Carcinoma

Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer

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