MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

Pang, Fei; Zha, Rujing; Zhao, Yingjun; Wang, Qifeng; Chen, Di; Zhang, Zhenfeng; Chen, Taoyang; Yao, Ming; Gu, Jianren; He, Xianghuo

doi:10.1371/journal.pone.0090867

Cited by 37 publications

(36 citation statements)

References 36 publications

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“…While a few reports do concern the overexpression of miR-525-3p and its role in liver cancer cell migration and invasion [29], none investigate this type of miRNA in LSCC or in head and neck cancers. The gene encodes miR-525 is reported to be located in a copy number amplified region 19q13.42.…”

Section: Discussionmentioning

confidence: 99%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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Abstract. BACKGROUND:Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers -and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS:We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.

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Section: Discussionmentioning

confidence: 99%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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“…Neomycin B is an FDA‐approved drug and used for the prevention of HE and bacterial infections caused by cirrhosis. Because upregulation of miR‐525 is observed in approximately 60% of liver cancer tissues and induces the migration and invasion of liver cancer cells by directly targeting ZNF395, neomycin B or its derivative may be a promising drug for the treatment of liver cancer patients. Velagapudi et al also succeeded in the synthesis of a small compound that binds to the Drosha processing site in the miR‐96 precursor.…”

Section: Drug Resistancementioning

confidence: 99%

Development of miRNA‐based therapeutic approaches for cancer patients

Takahashi

Prieto‐Vila

Kohama³

et al. 2019

Cancer Science

109

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Over the past few decades, si RNA and mi RNA have attracted a great deal of attention from researchers and clinicians. These molecules have been extensively studied from the standpoint of developing biopharmaceuticals against various diseases, including heart disease, diabetes and cancers. si RNA suppresses only a single target, whereas each mi RNA regulates the expression of multiple target genes. More importantly, because mi RNA are also secreted from cancer cells, and their aberrant expression is associated with tumor development and progression, they represent not only therapeutic targets but also promising biomarkers for diagnosis and prognosis. Therefore, mi RNA may be more effective tools against cancers, in which multiple signal pathways are dysregulated. In this review, we summarize recent progress in the development of mi RNA therapeutics for the treatment of cancer patients, and describe delivery systems for oligonucleotide therapeutics.

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“…(18) Importantly, Pang et al discovered that miR-525 is up-regulated in ~60% of liver cancer tissues and that these increased levels promote migration and invasion via down-regulation of ZNF395 . (15) Because of the urgent need for compounds to treat HCC, we studied if inhibition of miR-525 biogenesis by Neo-N 3 is sufficient to up-regulate ZNF395 levels. Indeed, Western blotting revealed a dose-dependent increase in ZNF-395 levels, with an ~1.7- and ~2-fold increase observed when cells were treated with 6.25 or 25 µM compound, respectively (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, miR-525 is overexpressed in ~60% of liver cancer tissues and indicates poor prognosis. (15) Overexpression of miR-525 enhances migratory and invasive properties via down-regulation of zinc finger protein 395 (ZNF395; also known as HDBP2). (15) Herein, we report that Neo-N 3 decreases levels of mature miR-525, up-regulates ZNF395, and inhibits the invasive properties of a hepatocellular carcinoma cell line.…”

mentioning

confidence: 99%

“…(15) Overexpression of miR-525 enhances migratory and invasive properties via down-regulation of zinc finger protein 395 (ZNF395; also known as HDBP2). (15) Herein, we report that Neo-N 3 decreases levels of mature miR-525, up-regulates ZNF395, and inhibits the invasive properties of a hepatocellular carcinoma cell line. Interestingly, other miRNAs predicted to bind the ZNF395 UTR are not affected by Neo-N 3 , showing that the compound’s effect can be traced to inhibition of miR-525.…”

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confidence: 99%

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Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma

Childs‐Disney

Disney

2015

ACS Chem. Biol.

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Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5″-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive properties to hepatocellular carcinoma (HCC) cells. Although HCC is one of the most common cancers, treatment options are limited, making the disease often fatal. Herein, we find that addition of 5″-azido neomycin B and its FDA-approved precursor, neomycin B, to an HCC cell line selectively inhibits production of the mature miRNA, boosts a downstream protein, and inhibits invasion. Interestingly, neomycin B is a second-line agent for hepatic encephalopathy (HE) and bacterial infections due to cirrhosis. Our results provocatively suggest that neomycin B, or second-generation derivatives, may be dual functioning molecules to treat both HE and HCC. Collectively, these studies show that rational design approaches can be tailored to disease-associated RNAs to afford potential lead therapeutics.

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MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

Cited by 37 publications

References 36 publications

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Development of miRNA‐based therapeutic approaches for cancer patients

Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma

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