MicroRNA-492 Is Processed From the Keratin 19 Gene and Up-Regulated in Metastatic Hepatoblastoma σ

Frowein, Julia von; Pagel, Philipp; Kappler, Roland; Schweinitz, Dietrich von; Roscher, Adelbert A.; Schmid, Irene

doi:10.1002/hep.24125

Cited by 70 publications

(63 citation statements)

References 38 publications

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“…Increasing evidences indicate that miR-492 has been shown to be one of the important determinants of cell tumorigenicity in multiple cancers [9][10][11]. However, the relationship between breast cancer and the expression of miR-492 has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

et al. 2014

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MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-492 plays an important role in cell tumorigenesis in multiple kinds of human cancer cells. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated miR-492's role in cell proliferation of breast cancer. MiR-492 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Overexpression of miR-492 promoted the proliferation and anchorage-independent growth of breast cancer cells. Bioinformatics analysis further revealed sex-determining region Y-box 7 (SOX7), a putative tumor suppressor, as a potential target of miR-492. Data from luciferase reporter assays showed that miR-492 directly binds to the 3'-untranslated region (3'-UTR) of SOX7 messenger RNA (mRNA) and repressed expression at both transcriptional and translational levels. Ectopic expression of miR-492 led to downregulation of SOX7 protein, which resulted in the upregulation of cyclin D1 and c-Myc. In functional assays, SOX7 silenced in miR-492-in-transfected ZR-75-30 cells has positive effect to promote cell proliferation, suggesting that direct SOX7 downregulation is required for miR-492-induced cell proliferation and cell cycle of breast cancer. In sum, these results suggest that miR-492 represents a potential onco-miR and participates in breast cancer carcinogenesis by suppressing SOX7 expression.

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Section: Introductionmentioning

confidence: 99%

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

et al. 2014

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“…They guide the association of the RNA‐induced silencing complex with target messenger RNAs (mRNAs), mostly through interactions with the 3′‐untranslated region (UTR), resulting in translational repression and/or mRNA destabilization 11, 12. Deregulation of miRNA biogenesis and expression is a hallmark of cancer12 and has been reported in HBL 13, 14, 15. Unlike small interfering RNAs (siRNAs), miRNAs can simultaneously target multiple genes involved in the same cellular pathways.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting β‐catenin and Wnt signaling

Indersie

Lesjean

Hooks

et al. 2017

Hepatology Communications

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Hepatoblastoma (HBL) is the most common pediatric liver cancer. In this malignant neoplasm, beta‐catenin protein accumulates and increases Wnt signaling due to recurrent activating mutations in the catenin‐beta 1 (CTNNB1) gene. Therefore, beta‐catenin is a key therapeutic target in HBL. However, controlling beta‐catenin production with therapeutic molecules has been challenging. New biological studies could provide alternative therapeutic solutions for the treatment of HBL, especially for advanced tumors and metastatic disease. In this study, we identified microRNAs (miRNAs) that target beta‐catenin and block HBL cell proliferation in vitro and tumor growth in vivo. Using our dual‐fluorescence‐FunREG system, we screened a library of 1,712 miRNA mimics and selected candidates inhibiting CTNNB1 expression through interaction with its untranslated regions. After validating the regulatory effect of nine miRNAs on beta‐catenin in HBL cells, we measured their expression in patient samples. Let‐7i‐3p, miR‐449b‐3p, miR‐624‐5p, and miR‐885‐5p were decreased in tumors compared to normal livers. Moreover, they inhibited HBL cell growth and Wnt signaling activity in vitro partly through beta‐catenin down‐regulation. Additionally, miR‐624‐5p induced cell senescence in vitro, blocked experimental HBL growth in vivo, and directly targeted the beta‐catenin 3′‐untranslated region. Conclusion: Our results shed light on how beta‐catenin‐regulating miRNAs control HBL progression through Wnt signaling inactivation. In particular, miR‐624‐5p may constitute a promising candidate for miRNA replacement therapy for HBL patients. (Hepatology Communications 2017;1:168‐183)

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“…Previous studies showed both consistent and inconsistent results regarding the correlation between miR-492 and the development of gastrointestinal cancers. It was reported that miR-492 could originate from the coding sequence of the hepatoblastoma marker gene keratin 19 (KRT19) and miR-492 along with its associated targets might serve as new hepatoblastoma biomarkers of clinical utility and could assist to explore targeted therapies, especially in metastatic hepatoblastoma with a poor prognosis [19]. However, there was an inconsistent report describing that the gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of colon cancer in European subjects [20].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-492 expression promotes the progression of hepatic cancer by targeting PTEN

Jiang

Zhang

et al. 2014

Cancer Cell Int

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BackgroundAberrant microRNA (miRNA) expression plays an essential role in the pathogenesis of Hepatocellular Carcinoma (HCC). However, specific involvement of miRNAs in HCC remains incompletely understood. The aim of this study was to explore the relevant microRNAs involved in the development of HCC.MethodsMicroRNA microarray was used to screen for the differentially expressed miRNAs in cancerous tissue and adjacent non-cancerous control tissue from patients with HCC (n = 3). Quantitative PCR was subsequently used to verify the results of microarray. Based on the findings, we investigated the role of miR-492 in the pathogenesis of HCC in vitro and in vivo using three tumor cells lines. Furthermore, we analyzed the clinical correlation of miR-492 expression with patient survival (n = 28).ResultsWe showed that microRNA-492 (miR-492) was elevated in HCC samples from patients with hepatic cancer. Knockdown of miR-492 attenuated the proliferation of cancer cell lines in vitro and inhibited primary tumor growth in vivo in SCID mice. We identified PTEN as a functional target for miR-492. Overexpression of miR-492 resulted in decreased PTEN expression and was associated with increased AKT activation in cancer cell lines. Moreover, miR-492-mediated increase of the proliferation of cancer cells was able to be suppressed by a PI3K inhibitor and an AKT inhibitor. The HCC patients with high miR-492/low PTEN had poorer survival.ConclusionsmiR-492 is implicated in the regulation of HCC progression through PTEN and AKT pathway. The data suggest that miR-492 is a biomarker of HCC and a potential therapeutic target for hepatocellular carcinoma.

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MicroRNA-492 Is Processed From the Keratin 19 Gene and Up-Regulated in Metastatic Hepatoblastoma σ

Cited by 70 publications

References 38 publications

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting β‐catenin and Wnt signaling

MicroRNA-492 expression promotes the progression of hepatic cancer by targeting PTEN

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