XIAP 3′-untranslated region serves as a competitor for HMGA2 by arresting endogenous let-7a-5p in human hepatocellular carcinoma

Wu, Wenyong; Tao, Si-Qi; Wang, Xiaonan; Lobie, Peter E.; Wu, Zhengsheng

doi:10.1177/1010428317719578

Cited by 5 publications

(3 citation statements)

References 53 publications

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“…Our results proposed combinations of let-7a-5p and miR-1246, let-7f-5p and miR-4532, miR-320c and let-7a-5p, miR-122-5p and let-7a-5p and the selected panel, namely, miR-320b/c and let-7a-5p, that showed the highest AUC of 0.9822. Of these three miRNAs, only let-7a-5p is supported by multiple studies indicating that let-7a-5p can modulate cell growth, migration and invasion, cell proliferation and apoptosis, and importantly, that it is associated with hepatis B and viral carcinogenesis, as indicated in Figure 4 [60][61][62][63][64]. In a Chinese cohort where 74.8% of patients were HBV positive, three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p and miR-425-5p) with an AUC of 0.905 were identified as promising biomarkers for identifying HCC patients [225].…”

Section: Discussionmentioning

confidence: 91%

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

Sartorius,

Winkler

et al. 2024

IJMS

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The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <−0.5 (p < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.

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Section: Discussionmentioning

confidence: 91%

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

Sartorius,

Winkler

et al. 2024

IJMS

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“…Our study proved, for the first time, that HMGA2 , a target gene of let-7a-5p, was 3.19-fold upregulated in the SAT of morbidly obese Chinese women. In previous studies, HMGA2 was confirmed to be a target gene of let-7a-5p, and the expression of HMGA2 was upregulated by arresting endogenous let-7a-5p [59]. In addition, the transfection of let-7 into 3T3-L1 cells could lead to a >3-fold decreased expression of HMGA2 [45].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Profiles in the Subcutaneous Adipose Tissues of Morbidly Obese Chinese Women

Wang¹,

Chen²,

Pan³

et al. 2021

Obes Facts

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Introduction: Obesity is a main global health issue and an outstanding cause of morbidity and mortality. Exploring miRNA profiling may help further studies on obesity. Methods: Three morbidly obese and 5 normal-weight Chinese women were enrolled in the microarray testing group. Abdominal subcutaneous adipose tissue (SAT) samples were excised. Total RNAs including miRNAs were extracted. Affymetrix GeneChip miRNA 4.0 Array was used to compare the expression profiles of miRNAs between the 2 groups. Two algorithms, miRanda and TargetScan, were used to predict target messenger RNAs (mRNAs). Bioinformatics analysis was then done based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The sample sizes were further expanded to 8 morbidly obese and 9 normal-weight subjects, and quantitative real-time PCR (qRT-PCR) was utilized to verify the expression of differential miRNAs and target genes. Results: As per the microarray assay, 58 miRNAs were differentially expressed in the SAT from the morbidly obese and normal-weight groups (Fold >4, p < 0.01, FDR <0.05); 54 of these were downregulated and 4 were upregulated in morbidly obese subjects. A total of 1,333 target genes were jointly predicted by miRanda and TargetScan. Further bioinformatics analysis showed that the differential miRNAs were involved in 269 significant biological functions and 89 significant signaling pathways. The validation experiment by qRT-PCR showed that the expression levels of miRNA-143-5p, miRNA-143-3p, miRNA-145-5p, and let-7a-5p were downregulated in morbidly obese subjects, consistent with the microarray detection. High-mobility group A2 (HMGA2), a target gene of the downregulated miRNA let-7a-5p, was first found to be upregulated 3.19-fold in the SAT of morbidly obese Chinese women when compared to normal-weight controls. Conclusions: MiRNA downregulation is a hallmark of intact SAT in a morbidly obese state. Transcription (DNA-dependent), small-molecule metabolic processes, the MAPK signaling pathway, and cancer-related pathways may play important roles in the occurrence and development of obesity. For the first time, we proved that HMGA2, a target gene of let-7a-5p, is upregulated in the SAT of morbidly obese Chinese women.

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“…Studies have shown that overexpression of miRNA let-7a-5p can inhibit the expression of X-linked inhibitor of apoptosis protein (XIAP) and high mobility protein A2 (HMGA2), thereby inhibiting the development and proliferation of liver cancer. 19 Through further analysis of qRT-PCR, we found that there is a significant negative correlation between miRNA let-7a-5p and BZW2 mRNA expression. We speculate that the decrease in the expression of miRNA let-7a-5p may partly explain the mechanism of the up-regulation of BZW2 expression in liver cancer tissues.…”

Section: Introductionmentioning

confidence: 85%

miR-let-7a-5p Inhibits Invasion and Migration of Hepatoma Cells by Regulating BZW2 Expression

Liu

Zhao

Peng

et al. 2020

OTT

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This study was performed to investigate the effect of miRNA let-7a-5p on the proliferation, invasion, and migration of human hepatoma cells as well as to determine BZW2 expression in these cells. Methods: Western blotting and real-time quantitative polymerase chain reaction were used to detect changes in the expression of miRNA let-7a-5p and BZW2 protein and gene, respectively. A luciferase reporter gene assay was used to examine whether BZW2 is the target gene of miR-let-7a-5p. The effect of miR-let-7a-5p on the invasion, migration, and proliferation of human hepatoma Bel-7404 and HepG2 cells was determined using the transwell invasion assay, scratch test, and CCK-8 assay, respectively. Flow cytometry was used to assess the effect of miR-let-7a-5p and BZW2 expression on apoptosis of hepatoma cells. Results: The luciferase reporter gene assay identified BZW2 as the target gene of miR-let-7a-5p. Moreover, increased expression of miR-let-7a-5p was found to significantly decrease BZW2 expression; inhibit proliferation, invasion, and migration; and promote apoptosis of hepatoma cells. Conclusion: miR-let-7a-5p can inhibit proliferation, invasion, and migration as well as promote apoptosis of hepatoma cells by decreasing BZW2 expression.

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XIAP 3′-untranslated region serves as a competitor for HMGA2 by arresting endogenous let-7a-5p in human hepatocellular carcinoma

Cited by 5 publications

References 53 publications

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

MicroRNA Expression Profiles in the Subcutaneous Adipose Tissues of Morbidly Obese Chinese Women

<p>miR-let-7a-5p Inhibits Invasion and Migration of Hepatoma Cells by Regulating <em>BZW2</em> Expression</p>

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