miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma

Tao, Zhonghua; Wan, Jie; Zeng, Lingyao; Xie, Lei; Sun, Hui‐Chuan; Qin, Lun–Xiu; Wang, Lu; Zhou, Jing; Ren, Zhenggang; Li, Yixue; Fan, Jia; Wu, Wei‐Zhong

doi:10.1083/jcb2006oia13

Cited by 25 publications

(30 citation statements)

References 12 publications

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“…10 and 11). In addition, both miRNAs have been shown to be expressed in human lung cells and to regulate a variety of cellular functions including splicing, translation, cell cycle, and cell differentiation (12,38,63). Further experiments using antagomirs in human alveolar type II cell cultures are likely to confirm this hypothesis.…”

Section: Effect Of Mir-183 On Sftpa1 and Sftpa2 Gene Expressionsupporting

confidence: 53%

An 11-nt sequence polymorphism at the 3′UTR of human SFTPA1 and SFTPA2 gene variants differentially affect gene expression levels and miRNA regulation in cell culture

Silveyra¹,

DiAngelo²,

Floros

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Silveyra P, DiAngelo SL, Floros J. An 11-nt sequence polymorphism at the 3=UTR of human SFTPA1 and SFTPA2 gene variants differentially affect gene expression levels and miRNA regulation in cell culture. Am J Physiol Lung Cell Mol Physiol 307: L106 -L119, 2014. First published May 2, 2014; doi:10.1152/ajplung.00313.2013.-Surfactant protein A (SP-A) plays a vital role in maintaining normal lung function and in host defense. Two genes encode SP-A in humans (SFTPA1, SFTPA2), and several gene variants have been identified for these. We have previously shown that sequence elements of SFTPA1 and SFTPA2 3= untranslated regions (UTRs) differentially affect translation efficiency in vitro. Polymorphisms at the 3=UTRs of mRNA variants may account for differential binding of miRNAs, a class of small noncoding RNAs that regulate gene expression. In this work, we generated 3=UTR reporter constructs of the SFTPA1 and SFTPA2 variants most frequently found in the population, as well as mutants of a previously described 11-nt indel element (refSNP rs368700152). Reporter constructs were transfected in NCI-H441 cells in the presence or absence of miRNA mimics, and reporter gene expression was analyzed. We found that human miRNA mir-767 negatively affected expression of constructs containing SFTPA1 and SFTPA2 variants, whereas mir-4507 affected only constructs with 3=UTRs of SFTPA1 variants 6A, 6A 3 , and 6A 4 (not containing the 11-nt element). Three miRNAs (mir-183, mir-449b, and mir-612) inhibited expression of recombinants of SFTPA2 variants and the SFTPA1 variant 6A 2 , all containing the 11-nt element. Similar results were obtained for SP-A expression when these miRNAs were transfected in Chinese hamster ovary cells expressing SFTPA1 or SFTPA2 variants or in NCI-H441 cells (genotype 1A 5 /1A 5 -6A 4 /6A 4 ). Moreover, transfection with a specific antagomir (antagomir-183) reversed the effects of mir-183 on SP-A mRNA levels. Our results indicate that sequence variability at the 3=UTR of SP-A variants differentially affects miRNA regulation of gene expression.

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Section: Effect Of Mir-183 On Sftpa1 and Sftpa2 Gene Expressionsupporting

confidence: 53%

An 11-nt sequence polymorphism at the 3′UTR of human SFTPA1 and SFTPA2 gene variants differentially affect gene expression levels and miRNA regulation in cell culture

Silveyra¹,

DiAngelo²,

Floros

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In addition, manipulation of HNRNPAB in HCC cells inversely affects E-cadherin expression. Some previous reports linked loss of E-cadherin expression with HCC cell invasion and metastasis (4,38,39). Thus, we postulate that HNRNPAB-dependent regulation of E-cadherin expression is a key mechanism that contributes to the underlying loss of epithelial architecture and thereby helps initiate invasion.…”

Section: Discussionmentioning

confidence: 84%

HNRNPAB Induces Epithelial–Mesenchymal Transition and Promotes Metastasis of Hepatocellular Carcinoma by Transcriptionally Activating SNAIL

et al. 2014

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Expression of heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) has been reported to be dysregulated in tumors, but its specific contributions to tumor formation and progression are not fully understood. Here, we demonstrate that HNRNPAB is overexpressed in highly metastatic cells and tumor tissues from patients with hepatocellular carcinoma (HCC) with recurrence. We found that HNRNPAB overexpression promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. RNA interference-mediated silencing of the EMT factor SNAIL attenuated HNRNPAB-enhanced cell invasion in vitro and lung metastasis in vivo. Mechanistically, HNRNPAB acted to transactivate SNAIL1 transcription, which in turn inhibited transcription of the pivotal SNAIL target gene E-cadherin. Overexpression of HNRNPAB in HCC samples correlated with higher SNAIL levels, shorter overall survival, and higher tumor recurrence. HNRNPAB overexpression, alone or in combination with SNAIL, was found to be a significant independent risk factor for recurrence and survival after curative resection. In conclusion, our findings define HNRNPAB as an activator of EMT and metastasis in HCC that predicts poor clinical outcomes. Cancer Res; 74(10); 2750-62. Ó2014 AACR.

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“…In addition, there are still other miRNAs that regulate the EMT process. For example, miR-612 has inhibitory effects on HCC migration, invasion and metastasis with one direct target, AKT2, through which EMT is inhibited [83]. The Eph tyrosine kinase receptor (EphA4) is one of target genes of miR-10a; by specifically targeting EphA4, miR-10a can act on invasion through EMT and on adhesion through the β1-integrin pathway in HCC cells [84].…”

Section: Deregulated Mirnas In Invasion and Metastasismentioning

confidence: 99%

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

Chu

Duan

et al. 2014

Cell Communication and Signaling

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The pathogenesis of hepatocellular carcinoma (HCC) is not fully understood, which has affected the early diagnosis and treatment of HCC and the survival time of patients. MicroRNAs (miRNAs) are a class of evolutionarily conserved small, non-coding RNAs, which regulate the expression of various genes post-transcriptionally. Emerging evidence indicates that the key enzymes involved in the miRNA biosynthesis pathway and some tumor-specific miRNAs are widely deregulated or upregulated in HCC and closely associated with the occurrence and development of various cancers, including HCC. Early studies have shown that miRNAs have critical roles in HCC progression by targeting many critical protein-coding genes, thereby contributing to the promotion of cell proliferation; the avoidance of apoptosis, inducing via angiogenesis; and the activation of invasion and metastasis pathways. Experimental data indicate that discovery of increasing numbers of aberrantly expressed miRNAs has opened up a new field for investigating the molecular mechanism of HCC progression. In this review, we describe the current knowledge about the roles and validated targets of miRNAs in the above pathways that are known to be hallmarks of HCC, and we also describe the influence of genetic variations in miRNA biosynthesis and genes.

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miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma

Cited by 25 publications

References 12 publications

An 11-nt sequence polymorphism at the 3′UTR of human SFTPA1 and SFTPA2 gene variants differentially affect gene expression levels and miRNA regulation in cell culture

An 11-nt sequence polymorphism at the 3′UTR of human SFTPA1 and SFTPA2 gene variants differentially affect gene expression levels and miRNA regulation in cell culture

HNRNPAB Induces Epithelial–Mesenchymal Transition and Promotes Metastasis of Hepatocellular Carcinoma by Transcriptionally Activating SNAIL

miRNAs affect the development of hepatocellular carcinoma via dysregulation of their biogenesis and expression

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