MiR-93-5p Promotes Cell Proliferation through Down-Regulating PPARGC1A in Hepatocellular Carcinoma Cells by Bioinformatics Analysis and Experimental Verification

Wang, Xinrui; Liao, Zhijun; Bai, Zhimin; He, Yan; Duan, Juan; Wei, Leyi

doi:10.3390/genes9010051

Cited by 34 publications

(24 citation statements)

References 46 publications

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“…miR-93-5p has been demonstrated to serve as an oncogene and promote tumor growth and metastasis in numerous types of cancer, including ovarian carcinoma (30), endometrial carcinoma (31), triple-negative breast cancer (32), gastric cancer (19), non-small cell lung cancer (11) and hepatocellular carcinoma (18). However, to the best of our knowledge, the physiological functions and underlying molecular mechanism of miR-93-5p in RB have not been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…miR-93-5p has been recently reported to promote the proliferation and metastasis of numerous human cancers, including hepatocellular carcinoma (18), non-small cell lung cancer (11) and gastric cancer (19); however, the functions of miR-93-5p in RB remain elusive. In the present study, it was revealed that miR-93-5p expression was significantly upregulated in RB tissues compared with in normal tissues.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‑93‑5p promotes the progression of human retinoblastoma by regulating the PTEN/PI3K/AKT signaling pathway

et al. 2018

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Numerous repor ts have indicated that microRNA-93-5p (miR-93-5p) is involved in the development and progression of human cancer, including non-small cell lung, gastric and breast cancer; however, the role of miR-93-5p in retinoblastoma (RB) remains unknown. In the present study, it was reported that miR-93-5p expression levels were significantly upregulated in RB tissues compared with in normal tissues by reverse transcription-quantitative polymerase chain reaction. Furthermore, it was demonstrated via cell counting kit-8 and Transwell assays that knockdown of miR-93-5p significantly suppressed the proliferation, migration and invasion of RB cells, but promoted cellular apoptosis. Regarding the underlying mechanism, the present study reported that phosphatase and tensin homolog (PTEN) was a direct target of miR-93-5p in RB cells. Overexpression of miR-93-5p significantly inhibited the expression of PTEN; opposing results were observed when PTEN expression was downregulated. Furthermore, the present study revealed that PTEN expression levels were downregulated and were inversely correlated with that of miR-93-5p in RB tissues. Additionally, the present study demonstrated that knockdown of PTEN in miR-93-5p-depleted RB cells significantly reversed the effects of miR-93-5p on cell proliferation, migration and invasion; miR-93-5p knockdown was suggested to promote PTEN expression, consequently inhibiting the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Collectively, the results of the present study demonstrated that miR-93-5p may serve a role as an oncogene by modulating the PTEN/PI3K/AKT signaling pathway in RB, indicating that miR-93-5p may be a potential therapeutic target for the treatment of RB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA‑93‑5p promotes the progression of human retinoblastoma by regulating the PTEN/PI3K/AKT signaling pathway

et al. 2018

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“…Suppression of miR‐93 caused contrary results. Wang et al found that, in patients with hepatocellular carcinoma, miR‐93‐5p can directly target 3'‐UTR in the mRNA of PPARGC1A (also known as PGC‐1a), inhibiting the expression of PPARGC1A, which functions as a coactivator of transcription and a metabolic modulator. Yang et al revealed the relationships between miR‐93‐5p expression and the overall survival rate of patients with non‐small cell lung carcinoma (NSCLC).…”

Section: Discussionmentioning

confidence: 99%

Expression significance and potential mechanism of hypoxia‐inducible factor 1 alpha in patients with myelodysplastic syndromes

Liang

Luo

et al. 2019

Cancer Medicine

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Objective To investigate the expression level and potential mechanism of hypoxia‐inducible factor 1 alpha (HIF‐1α) in patients with myelodysplastic syndromes (MDS). Methods Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF‐1α in paraffin‐embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF‐1α and clinical parameters were examined. To further investigate the significance of HIF‐1α expression in MDS patients, the researchers not only extracted the data about HIF‐1α expression from MDS‐related microarrays but also analyzed the correlation between the level of HIF‐1α expression and MDS. The microRNA (miRNA) targeting HIF‐1α was predicted and verified with a dual luciferase experiment. Results Immunohistochemistry revealed that the positive expression rate of HIF‐1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF‐1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF‐1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF‐1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR‐93‐5p had a site for binding with HIF‐1α, and a dual luciferase experiment confirmed that miR‐93‐5p could bind with HIF‐1α. Conclusion The upregulated expression of HIF‐1α was examined in the myeloid tissues of MDS patients. The presence of HIF‐1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR‐93‐5p could bind to HIF‐1α by targeting, showing its potential to be the target of HIF‐1α in MDS.

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“…For example, a series of experiments conducted in hepatoma cells have found miR-93-5p to be upregulated and act as a promoter of cell proliferation. Furthermore, the inverse correlation between miR-93-5p and PPARGC1A gene expression was validated in the TCGA liver cancer data [4]. Mature miRNAs are highly stable and have great utility as biomarkers of diagnosis/ prognosis and disease progression.…”

Section: Introductionmentioning

confidence: 92%

Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model

et al. 2020

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Background: The established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies. Methods: The HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level. Results: mRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TCGA data are previously reported in the literature and overlap in regulation and function, new pairs have been identified that may contribute to the discovery of novel targets. Conclusion: The results strongly support the hypothesis that miRNAs are important regulators of mRNAs in HCC. Furthermore, these results emphasize the biological relevance of studying miRNA-mRNA pairs.

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MiR-93-5p Promotes Cell Proliferation through Down-Regulating PPARGC1A in Hepatocellular Carcinoma Cells by Bioinformatics Analysis and Experimental Verification

Cited by 34 publications

References 46 publications

MicroRNA‑93‑5p promotes the progression of human retinoblastoma by regulating the PTEN/PI3K/AKT signaling pathway

MicroRNA‑93‑5p promotes the progression of human retinoblastoma by regulating the PTEN/PI3K/AKT signaling pathway

Expression significance and potential mechanism of hypoxia‐inducible factor 1 alpha in patients with myelodysplastic syndromes

Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model

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