Significance of Dysregulated Metadherin and MicroRNA-375 in Head and Neck Cancer

Hui, Angela Bik‐Yu; Bruce, Jeff; Alajez, Nehad M.; Shi, Wei; Yue, Shi‐Jun; Perez-Ordonez, Bayardo; Xu, Wei; O’Sullivan, Brian; Waldron, John; Cummings, Bernard; Gullane, Patrick; Siu, Lillian L.; Liu, Fei‐Fei

doi:10.1158/1078-0432.ccr-11-2102

Cited by 81 publications

(64 citation statements)

References 51 publications

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“…We have conducted global miRNA profiling of HNSCC (5), through which the miR-375$metadherin axis was newly identified as a potentially important pathway that could partially explain the propensity for lung metastases in this disease (6). Additional miRNA studies in HNSCC have reported potentially predictive sets of miR-205 and let-7d or miR-210 as a hypoxia marker (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Hui

Lin

et al. 2013

Clinical Cancer Research

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104

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Purpose: Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status.Methods: Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls.Results: Overall, 224 miRNAs were expressed in more than 80% of the investigated samples, with 128 (57%) being significantly differentially expressed between tumor versus normal tissues (P < 0.05). Upregulated miR-20b, miR-9, and miR-9 Ã were significantly associated with HPV/p16-status. Three miRNA sets were significantly associated with overall survival (miR-107, miR-151, miR-492; P ¼ 0.0002), diseasefree survival (miR-20b, miR-107, miR-151, miR-182, miR-361; P ¼ 0.0001), and distant metastasis (miR-151, miR-152, miR-324-5p, miR-361, miR492; P ¼ 0.0087), which retained significance even after adjusting for p16 status. The associated biologic functions of these miRNAs include immune surveillance, treatment resistance, invasion, and metastasis. Conclusion: We have identified several miRNAs, which associate with HPV status in OPC; furthermore, three candidate prognostic sets of miRNAs seem to correlate with clinical outcome, independent of p16 status. Furthermore, evaluations will offer biologic insights into the mechanisms underlying the differences between HPV-positive versus HPV-negative OPC.

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Section: Introductionmentioning

confidence: 99%

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Hui

Lin

et al. 2013

Clinical Cancer Research

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104

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“…188 MiR-375 targets metadherin (MTDH) [189][190][191][192][193] and miR-504 targets forkhead box P1 (FOXP1), 194 also important for invasion. Finally, there is a small group of targets whose direct function in invasion are unclear, such as programmed cell death 4 (PDCD4), 195 targeted by miR-21, BCL2 binding component 3 (BBC3), 196 and mitochondrial superoxide dismutase 2 (SOD2), 197 targeted by miR-222.…”

mentioning

confidence: 99%

Mechanisms of Invasion in Head and Neck Cancer

Jimenez¹,

Jayakar²,

Ow³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-The highly invasive properties demonstrated by head and neck squamous cell carcinoma (HNSCC) are often associated with locoregional recurrence and lymph node metastasis in patients and is a key factor leading to an expected 5-year survival rate of approximately 50% for patients with advanced disease. It is important to understand the features and mediators of HNSCC invasion so that new treatment approaches can be developed.Objectives.-To provide an overview of the characteristics, mediators, and mechanisms of HNSCC invasion.Data Sources.-A literature review of peer-reviewed articles in PubMed on HNSCC invasion.Conclusions.-Histologic features of HNSCC tumors can help predict prognosis and influence clinical treatment decisions. Cell surface receptors, signaling pathways, proteases, invadopodia function, epithelial-mesenchymal transition, microRNAs, and tumor microenvironment are all involved in the regulation of the invasive behavior of HNSCC cells. Identifying effective HNSCC invasion inhibitors has the potential to improve outcomes for patients by reducing the rate of spread and increasing responsiveness to chemoradiation.

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“…16 Very interestingly, another group also reported that MTDH was regulated by miR-375 and that both miR-375 overexpression and MTDH knockdown in HNSCC cell lines resulted in significant decreases in tumor formation in SCID mice. 24 In ESCC, expression signatures revealed that miR-375 was significantly reduced in cancer cells. 12,22,23 The downregulation of miR-375 was caused by hypermethylation of the promoter region, and ectopic expression of miR-375 inhibited tumor cell growth and metastasis in vitro and in vivo by targeting insulin-like growth factor 1 receptor.…”

Section: Aberrant Expression and Functional Significance Of Mir-375 Imentioning

confidence: 99%

“…16,17,[23][24][25][26][27][28][29][30][31][39][40][41][42] Downregulation of miR-375 has been reported for gastric cancer, cervical cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma. 26,27,29,30,[43][44][45] In gastric cancer, ectopic expression of miR-375 in cancer cells reduced cell viability and induced apoptosis by targeting PDK1 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein z (YWHAZ).…”

Section: Aberrant Expression Of Mir-375 and Its Target Genes In Othermentioning

confidence: 99%

“…16,17 Other research groups also showed downregulation of miR-375 in HNSCC and ESCC and other types of human cancers. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] In this review, we focus on HNSCC and ESCC and describe the aberrant expression of miRNAs in these cancers and the cancer pathways they may regulate in these diseases.…”

Section: Introductionmentioning

confidence: 99%

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The functional significance of microRNA-375 in human squamous cell carcinoma: aberrant expression and effects on cancer pathways

et al. 2012

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MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules consisting of 19-22 nucleotides that are involved in a variety of biological processes, including development, differentiation, apoptosis and cell proliferation. In cancer research, a growing body of evidence has indicated that miRNAs are aberrantly expressed in many types of human cancers and can function either as tumor suppressors or oncogenes. Bioinformatic predictions suggest that miRNAs regulate more than 30% of protein-coding genes. Aberrant expression of miRNAs in cancer cells causes destruction of miRNA-regulated messenger RNA networks. Therefore, the identification of miRNA-regulated cancer pathways is important for understanding the molecular mechanisms of human cancer. Searching for the aberrant expression of miRNAs in cancer cells is the first step in the functional analysis of miRNAs in cancer cells. Genome-wide miRNA expression signatures can rapidly and precisely reveal aberrant expression of miRNA in cancers. The miRNA expression signatures of human cancers have revealed that miR-375 is significantly downregulated in cancer cells. Our recent data on maxillary sinus, hypopharyngeal and esophageal squamous cell carcinomas have suggested that miR-375 is frequently downregulated and functions as a tumor suppressor that targets several oncogenic genes in cancer cells. In this review, we focus on several types of human squamous cell carcinoma and describe the aberrant expression of miRNAs and the cancer pathways they regulate in these diseases.

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Significance of Dysregulated Metadherin and MicroRNA-375 in Head and Neck Cancer

Cited by 81 publications

References 51 publications

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Potentially Prognostic miRNAs in HPV-Associated Oropharyngeal Carcinoma

Mechanisms of Invasion in Head and Neck Cancer

The functional significance of microRNA-375 in human squamous cell carcinoma: aberrant expression and effects on cancer pathways

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