mir-182-5p Regulates Cell Growth of Liver Cancer via Targeting RCAN1

Zheng, Jianxing; Wu, Dongyang; Wang, Libing; Qu, Fengzhi; Cheng, Daming; Liu, Xiaogang

doi:10.1155/2021/6691305

Cited by 7 publications

(7 citation statements)

References 41 publications

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“…For those with liver cancer, miR-182-5p overexpression has been shown to have diagnostic and prognostic relevance ( 52 ). In concordance with our results, in liver cancer tissues and cell lines, miR-182-5p was recently found to be substantially expressed, according to a study ( 53 ). MiR-182-5p stimulated liver cancer cell proliferation by downregulating the regulator of calcineurin 1 (RCAN1).…”

Section: Discussionsupporting

confidence: 93%

miRNome of Child A hepatocellular carcinoma in Egyptian patients

et al. 2023

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IntroductionHepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes.MethodsAdvances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC.Results & discussionIn this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in “pathways in cancer and PI3K-Akt signaling pathway” KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC.

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Section: Discussionsupporting

confidence: 93%

miRNome of Child A hepatocellular carcinoma in Egyptian patients

et al. 2023

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“…MiR-182-5p is a high-priority miRNA in HCC, and is closely associated with early recurrence and overall survival in patients ( 21 , 22 ). Numerous studies have shown that miR-182-5p is dramatically overexpressed in HCC and could enhance the ability of migration, invasion, adhesion and proliferation of HCC cells via repressing multiple targeting genes, such as FOXO3a ( 21 ), Hepatitis C virus p7 trans-regulated protein 3 (P7TP3) ( 23 ), and regulator of calcineurin 1 (RCAN1) ( 24 ). Furthermore, high-throughput sequencing has revealed that miR-182-5p expression is dramatically increased in fatty liver-related fibrosis ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analyses Identify Key Molecules and Reveal the Potential Mechanism of miR-182-5p/FOXO1 Axis in Alcoholic Liver Disease

Zuo

Zeng

et al. 2021

Front. Med.

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Background: Alcoholic liver disease (ALD) is one of the most common chronic liver diseases worldwide. However, the potential molecular mechanism in ALD development remains unclear. The objective of this work was to identify key molecules and demonstrate the underlying regulatory mechanisms.Methods: RNA-seq datasets were obtained from Gene Expression Omnibus (GEO), and key molecules in ALD development were identified with bioinformatics analysis. Alcoholic liver disease mouse and cell models were constructed using Lieber-DeCarli diets and alcohol medium, respectively. Quantitative real-time PCR and Western blotting were conducted to confirm the differential expression level. Dual-luciferase reporter assays were performed to explore the targeting regulatory relationship. Overexpression and knockdown experiments were applied to reveal the potential molecular mechanism in ALD development.Results: Between ALD patients and healthy controls, a total of 416 genes and 21 microRNAs (miRNAs) with significantly differential expression were screened. A comprehensive miRNA-mRNA network was established; within this network, the miR-182-5p/FOXO1 axis was considered a significant pathway in ALD lipid metabolism. Mouse and cell experiments validated that miR-182-5p was substantially higher in ALD than in normal livers, whereas the expression of FOXO1 was dramatically decreased by alcohol consumption (P < 0.05). Next, dual-luciferase reporter assays demonstrated that miR-182-5p directly targets the binding site of the FOXO1 3′UTR and inhibits its mRNA and protein expression. In addition, miR-182-5p was found to promote hepatic lipid accumulation via targeting the FOXO1 signaling pathway, and inhibition of the miR-182-5p/FOXO1 axis improved hepatic triglyceride (TG) deposition in ALD by regulating downstream genes involved in lipid metabolism.Conclusion: In summary, key molecules were identified in ALD development and a comprehensive miRNA–mRNA network was established. Meanwhile, our results suggested that miR-182-5p significantly increases lipid accumulation in ALD by targeting FOXO1, thereby providing novel scientific insights and potential therapeutic targets for ALD.

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“…Numerous studies demonstrated that microRNAs (miRNAs) negatively regulate RNA targets at the post-transcriptional level (Cheng et al 2015 ). In HCC, oncogenic miRNAs, including miR-877, miR‐572, and miR-182-5p, negatively regulate RCAN1 to promote HCC progression (Zheng et al 2021 ; Song et al 2019 ; Shi et al 2018 ). Thus, RCAN1 expression was reduced in primary HCC compared to adjacent non-cancer liver tissues (Zheng et al 2021 ; Song et al 2019 ; Shi et al 2018 ).…”

Section: Rcan1 Expression Regulation and Function In Cancermentioning

confidence: 99%

“…In HCC, oncogenic miRNAs, including miR-877, miR‐572, and miR-182-5p, negatively regulate RCAN1 to promote HCC progression (Zheng et al 2021 ; Song et al 2019 ; Shi et al 2018 ). Thus, RCAN1 expression was reduced in primary HCC compared to adjacent non-cancer liver tissues (Zheng et al 2021 ; Song et al 2019 ; Shi et al 2018 ). The inhibitory effect of RCAN1 in HCC was further refined to its subtype RCAN1.4 (Jin et al 2017 ).…”

Section: Rcan1 Expression Regulation and Function In Cancermentioning

confidence: 99%

“…In addition, the RCAN1.1 promoter region contains a functional GRE, and RCAN1.1 is upregulated by glucocorticoids at the transcriptional level (Yang et al 2000 ; Nagao et al 2012 ). Some tumor-derived exosome (TEX) miRNAs can promote angiogenesis and metastasis of tumors by inhibiting RCAN1 (Kim et al 2020 ; Zheng et al 2021 ; Zhang et al 2020 ). Super-enhancers (SEs) are defined as large clusters of transcriptional enhancers and are found in the RCAN1.4 sequences.…”

Section: Introductionmentioning

confidence: 99%

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RCAN1-mediated calcineurin inhibition as a target for cancer therapy

Lao

Zhang

Yang

et al. 2022

Mol Med

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Cancer is the leading cause of mortality worldwide. Regulator of calcineurin 1 (RCAN1), as a patent endogenous inhibitor of calcineurin, plays crucial roles in the pathogenesis of cancers. Except for hypopharyngeal and laryngopharynx cancer, high expression of RCAN1 inhibits tumor progression. Molecular antitumor functions of RCAN1 are largely dependent on calcineurin. In this review, we highlight current research on RCAN1 characteristics, and the interaction between RCAN1 and calcineurin. Moreover, the dysregulation of RCAN1 in various cancers is reviewed, and the potential of targeting RCAN1 as a new therapeutic approach is discussed.

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mir-182-5p Regulates Cell Growth of Liver Cancer via Targeting RCAN1

Cited by 7 publications

References 41 publications

miRNome of Child A hepatocellular carcinoma in Egyptian patients

miRNome of Child A hepatocellular carcinoma in Egyptian patients

Integrated Analyses Identify Key Molecules and Reveal the Potential Mechanism of miR-182-5p/FOXO1 Axis in Alcoholic Liver Disease

RCAN1-mediated calcineurin inhibition as a target for cancer therapy

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