miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma

Nohata, Nijiro; Sone, Yaeko; Hanazawa, Toyoyuki; Fuse, Miki; Kikkawa, Naoko; Yoshino, Hirofumi; Chiyomaru, Takeshi; Kawakami, Kazumori; Enokida, Hideki; Nakagawa, Masayuki; Shozu, Makio; Okamoto, Yoshitaka; Seki, Naohiko

doi:10.18632/oncotarget.213

Cited by 161 publications

(173 citation statements)

References 36 publications

(55 reference statements)

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“…39 MiR-1, miR-133a, and miR-133b have been reported as significantly under-represented in leiomyosarcoma 40 and rhabdomyosarcoma. 11 There are reports of miR-1 in epithelial malignancies including non-small cell lung cancer, head and neck squamous cell carcinoma, and hepatocellular carcinoma, [41][42][43] but this has not yet been microRNA expression in human sarcomas PY Yu et al reported in non-myogenic sarcomas. The downregulation of miR-1 appeared to correlate inversely with the upregulation of Met in both non-small cell lung cancers and hepatocellular carcinomas.…”

Section: Discussionmentioning

confidence: 99%

“…In head and neck squamous cell carcinomas, miR-1 acts as a tumor suppressor by directly targeting transgelin-2, suggesting possible oncogenic pathways in the pathogenesis of head and neck squamous cell carcinoma. 42 Another miRNA of interest is miR-29. This miR functions as a positive regulator of myogenesis through feedback inhibition of YY1 and also functions as a tumor suppressor in rhabdomyosarcoma.…”

Section: Discussionmentioning

confidence: 99%

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A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas

Balkhi

Ladner

et al. 2016

Laboratory Investigation

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Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue. Five histologic types were examined that included: myxoid liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, and synovial sarcoma. In addition, soft-tissue lipomas and normal fat were included as a separate set of controls for the lipogenic tumors. Clustering analysis showed a distinct global difference in expression patterns between the normal and sarcoma tissues. Expression signatures in an unsupervised hierarchical clustering analysis revealed tight clustering in synovial and myxoid liposarcomas, and the least clustering was observed in the pleomorphic rhabdomyosarcoma subtype. MiR-145 showed underexpression in pleomorphic rhabdomyosarcoma, well-differentiated liposarcoma, and synovial sarcoma. Unexpectedly, we found that a set of muscle-specific microRNAs (miRNAs; myomiRs): miR-133, miR-1, and miR-206 was significantly underexpressed in well-differentiated liposarcoma and synovial sarcoma, suggesting that they may function as tumor suppressors as described in muscle-relevant rhabdomyosarcomas. In addition, a tight linear progression of miRNA expression was identified from normal fat to dedifferentiated liposarcoma. These results suggest that miRNA expression profiles could elucidate classes of miRNAs that may elicit tumor-relevant activities in specific sarcoma subtypes. Sarcomas are rare malignant heterogeneous tumors of mesenchymal derivation with over 50 histologic types described. 1 The pathogenesis and biology of many of the different histologic subtypes remain poorly understood. Recent progress in understanding the biology of sarcomas has identified distinct molecular and pathologic entities within these heterogeneous groups of tumors that have paved the way for development of targeted therapies. There are emerging data that seem to suggest that miRNA might be a driver in sarcomagenesis with potential therapeutic implications. microRNAs (miRNAs) are non-coding strands of RNA of 22 nucleotides in length that regulate the expression of genes involved in processes such as development, differentiation, cell proliferation, metabolism, cell death, viral infection, and cancer. 2,3 They have a broad effect through base pairing with mRNA at their 3′ untranslated region to inhibit translation or to target the mRNA for degradation. Bioinformatics predictions have shown that miRNAs regulatẽ 30% of mammalian protein-coding genes. Their role in the molecular biology of cancers is well-established partly

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas

Balkhi

Ladner

et al. 2016

Laboratory Investigation

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“…Cell invasion assays were carried out using modified Boyden chambers consisting of Transwellprecoated Matrigel membrane filter inserts with 8-mm pores in 24-well tissue culture plates (BD Biosciences, Bedford, MA, USA), as described previously. 22 Screening of miR-143-and miR-145-regulated genes: Pathway analysis using databases. The predicted target genes and their miRNA binding site seed regions were investigated using TargetScan (release 6.2, http://www.targetscan.org/).…”

Section: Methodsmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are endogenous small ncRNA molecules (19)(20)(21)(22) bases in length) that regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. (5) Currently, 2578 human mature miRNAs are registered at miRBase (release 20, June 2013; http://www.mirbase.org/).…”

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confidence: 99%

Tumor‐suppressive microRNA‐143/145 cluster targets hexokinase‐2 in renal cell carcinoma

et al. 2013

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Our recent studies of microRNA (miRNA) expression signatures have indicated that the miR-143/145 cluster is significantly downregulated in several types of cancer and represents a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of the miR-143/145 cluster in cancer cells and to identify novel molecular targets of the miR-143/145 cluster in renal cell carcinoma (RCC). The expression levels of miR-143 and miR-145 were significantly downregulated in RCC tissues compared with adjacent non-cancerous tissues. A significant positive correlation was recognized between miR-143 and miR-145 expression. Restoration of mature miR-143 or miR-145 in 786-O and A498 RCC cells revealed that both mature miRNAs significantly inhibited cancer cell proliferation and invasion, suggesting that the miR-143/145 cluster functioned as a tumor suppressor in RCC. Gene expression data and in silico database analysis showed that the hexokinase-2 (HK2) gene, which encodes a glycolytic enzyme crucial for the Warburg effect in cancer cells, was a candidate target of the miR-143/145 cluster. Luciferase reporter assays showed that both miR-143 and miR-145 directly regulated HK2. In RCC clinical specimens, the expression of HK2 was significantly higher in cancer tissues than in non-cancerous tissues. Silencing HK2 suppressed RCC cell proliferation and invasion, suggesting that HK2 has oncogenic functions in RCC. Thus, our data showed that loss of the tumor-suppressive miR-143/145 cluster enhanced RCC cell proliferation and invasion through targeting HK2. (Cancer Sci 2013; 104: 1567-1574 R enal cell carcinoma (RCC) is a disease in which cancer cells form in the tubules of the kidney. Globally, the incidence and mortality rates of RCC are increasing 2-3% per decade.(1) The 5-year survival rate of advanced-stage RCC is very poor (5-10%) due to recurrence or distant metastasis.(2)The latest treatment for RCC includes molecular targeted therapies, which have been developed and are being widely used for patients with metastatic or recurrent RCC. However, these types of therapies are not expected to have curative effects. Therefore, to improve outcomes in patients with RCC, it is necessary to fully elucidate the molecular mechanisms of RCC.The discovery of non-coding RNAs (ncRNAs) in the human genome was an important conceptual breakthrough in the postgenome sequencing era, (4) and it is now evident that improved understanding of ncRNAs is necessary for continued progress in cancer research. MicroRNAs (miRNAs) are endogenous small ncRNA molecules (19-22 bases in length) that regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs are unique in their ability to regulate multiple protein-coding genes and are predicted to regulate more than 60% of the protein-coding genes in the human genome. (6) A growing body of evidence suggests that miRNAs are aberrantly expressed in many human cancers and that they play signif...

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“…Downregulation of miR-206 was previously found to contribute to laryngeal cancer proliferation and invasion via regulation of VEGF expression (34), while VEGF was reported to be a predictor for HNSCC (35), implying that miR-206 may be an inhibitor for HNSCC. A previous study found that miR-1 inhibited cell proliferation of HNSCC by targeting TAGLN2 (36), and downregulation of miR-153 promoted tumor metastasis in human epithelial cancer by targeting ZEB2 (37). On the other hand, nucleotide biosynthesis is involved with tumor cell growth during cell proliferation (38).…”

Section: Discussionmentioning

confidence: 99%

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

Zhang²,

Xia

et al. 2015

Oncology Reports

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Abstract. The aim of the present study was to explore the potential mechanisms involved in each subtype of head and neck squamous cell carcinoma (HNSCC) via subpath analysis and to investigate their relevance in the prevention of HNSCC. Gene expression profiles of GSE6631 and GSE39366 containing 44 and 168 HNSCC samples, respectively, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from samples in GSE6631 and GSE393666 were screened using the Detection of Imbalanced Differential Signal (DIDS) method respectively. DEGs in GSE39366 were matched with the DEGs in GSE6631 and were used to classify the subtypes of HNSCC based on hierarchical clustering analysis. Furthermore, DEGs were separated into different subtypes and then the pathway information was analyzed. The regulated miRNAs for the DEGs in each subtype were analyzed to select the significant subpaths. Totally, 1,095 DEGs from GSE6631 and 2,528 DEGs from GSE39366 were screened. Samples in GSE39366 were separated into four subtypes. Specific genes in each subtype and DEGs in the common gene set involved in a variety of pathways were identified. In addition, the significant miRNAtarget-pathway subpath of each subtype of HNSCC and the common gene set of HNSCC were also enriched. Our data suggest that human papillomavirus (HPV) is positively correlated with HNSCC in subtype 2. Several miRNAs (miRLet-7A, miR-1, miR-206, miR-153, miR-519A and miR-506) and their target genes (CYP46A1, BPNT1, MCM7 and COL5A1) are crucial for HNSCC prevention via different pathways and may provide further knowledge of the mechanisms involved in the progression of HNSCC.

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miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma

Cited by 161 publications

References 36 publications

A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas

A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas

Tumor‐suppressive microRNA‐143/145 cluster targets hexokinase‐2 in renal cell carcinoma

Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways

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