Lowered expression of microRNA-125a-5p in human hepatocellular carcinoma and up-regulation of its oncogenic targets sirtuin-7, matrix metalloproteinase-11, and c-Raf

Coppola, Nicola; Stefano, G. de; Panella, Marta; Onorato, Lorenzo; Iodice, V.; Minichini, Carmine; Mosca, Nicola; Desiato, L.; Farella, Nunzia; Starace, Mario; Liorre, G.; Potenza, Nicoletta; Sagnelli, E.; Russo, Andrew F.

doi:10.18632/oncotarget.15809

Cited by 34 publications

(19 citation statements)

References 69 publications

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“…It has also been demonstrated that the deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC[ 121 ], while its re-expression reduced disease manifestations and tumor incidence[ 122 ]. We recently reported a lower expression of miR-125a-5p in HCC tissues compared with non-tumor tissue in 55 patients with hepatocellular cancer of different etiologies[ 123 ]. In addition, we found a significant upregulation of three oncogenes in HCC tissue, MMP-11, c-Raf and Sirt-7, already validated as molecular targets of miR-125a-5p, an observation that provides an explanation for the tumor suppressor activity exerted by this microRNA.…”

Section: Micrornas As Biomarkers Of Hbv-related Liver Diseasesmentioning

confidence: 99%

Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

Sagnelli

Potenza

Onorato

et al. 2018

WJH

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MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level by affecting both the stability and translation of complementary mRNAs. Several studies have shown that miRNAs are important regulators in the conflicting efforts between the virus (to manipulate the host for its successful propagation) and the host (to inhibit the virus), culminating in either the elimination of the virus or its persistence. An increasing number of studies report a role of miRNAs in hepatitis B virus (HBV) replication and pathogenesis. In fact, HBV is able to modulate different host miRNAs, particularly through the transcriptional transactivator HBx protein and, conversely, different cellular miRNAs can regulate HBV gene expression and replication by a direct binding to HBV transcripts or indirectly targeting host factors. The present review will discuss the role of miRNAs in the pathogenesis of HBV-related diseases and their role as a biomarker in the management of patients with HBV-related disease and as therapeutic targets.

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Section: Micrornas As Biomarkers Of Hbv-related Liver Diseasesmentioning

confidence: 99%

Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

Sagnelli

Potenza

Onorato

et al. 2018

WJH

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“…MircroRNA-125a-5p (miR-125a), denominated lin-4 in nematodes, is of special interest, since it is very well conserved in evolution 16 and plays a pivotal role in development and cell differentiation 1 , 17 – 20 . Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, including breast 21 – 23 , gastric 24 , cervical 25 , lung 26 , 27 , ovarian 28 , and colon 29 cancers, retinoblastoma 30 , medulloblastoma 31 , glioblastoma 32 , neuroblastoma 33 , and hepatocellular carcinoma 34 – 36 .…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms governing microRNA-125a expression in human hepatocellular carcinoma cells

Potenza

Panella

Castiello

et al. 2017

Sci Rep

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MicroRNA-125a-5p (miR-125a) is a vertebrate homolog of lin-4, the first discovered microRNA, and plays a fundamental role in embryo development by downregulating Lin-28 protein. MiR-125a is also expressed in differentiated cells where it generally acts as an antiproliferative factor by targeting membrane receptors or intracellular transductors of mitogenic signals. MiR-125a expression is downregulated in several tumors, including hepatocellular carcinoma (HCC) where it targets sirtuin-7, matrix metalloproteinase-11, VEGF-A, Zbtb7a, and c-Raf. In this study, we have isolated the transcription promoter of human miR-125a and characterized its activity in HCC cells. It is a TATA-less Pol II promoter provided with an initiator element and a downstream promoter element, located 3939 bp upstream the genomic sequence of the miRNA. The activity of the promoter is increased by the transcription factor NF-kB, a master regulator of inflammatory response, and miR-125a itself was found to strengthen this activation through inhibition of TNFAIP3, a negative regulator of NF-kB. This finding contributes to explain the increased levels of miR-125a observed in the liver of patients with chronic hepatitis B.

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“…miR‐125a is an acknowledged miRNA for suppressor genes. It plays a tumor suppressing part in tumors such as gastric cancer and liver cancer .…”

Section: Discussionmentioning

confidence: 99%

Bilobalide alleviates IL‐17‐induced inflammatory injury in ATDC5 cells by downregulation of microRNA‐125a

Mao

Zhang

et al. 2019

J Biochem & Molecular Tox

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Ankylosing spondylitis (AS) is a high disability and greatly destructive disease. In this study, we preliminarily studied the function and mechanism of bilobalide (BIL) on interleukin (IL)‐17‐induced inflammatory injury in ATDC5 cells. CCK‐8 and migration assays were used to detect the functions of IL‐7, BIL, and microRNA (miR)‐125a on cell viability and migration. The miR‐125a level was changed by transfection, and tested by real‐time quantitative polymerase chain reaction. Additionally, Western blot tested the levels of inflammatory factors (IL‐6 and tumor necrosis factor‐α), matrix metalloproteinases (MMPs), and pathway‐related proteins. Moreover, the enzyme‐linked immunosorbent assay also was used to detect inflammatory factor levels. IL‐7 was used to construct an inflammatory injury model in ATDC5 cells. Based on this, BIL inhibited IL‐17‐induced cell viability, migration, and expressions of inflammatory factors and MMPs. Furthermore, we found BIL negatively regulated miR‐125a, and the miR‐125a mimic could partly reverse the effects of BIL on IL‐17‐injury. Finally, we showed that BIL inhibited the c‐Jun N‐terminal kinase (JNK) and nuclear factor kappa B (NF‐κB) pathways, and the miR‐125a mimic had the opposite effect. BIL inhibited IL‐17‐induced inflammatory injury in ATDC5 cells by downregulation of miR‐125a via JNK and NF‐κB signaling pathways.

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Lowered expression of microRNA-125a-5p in human hepatocellular carcinoma and up-regulation of its oncogenic targets sirtuin-7, matrix metalloproteinase-11, and c-Raf

Cited by 34 publications

References 69 publications

Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

Molecular mechanisms governing microRNA-125a expression in human hepatocellular carcinoma cells

Bilobalide alleviates IL‐17‐induced inflammatory injury in ATDC5 cells by downregulation of microRNA‐125a

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