A miR-centric view of head and neck cancers

Babu, Janki Mohan; Prathibha, R.; Jijith, V.S.; Hariharan, Ramkumar; Pillai, M. Radhakrishna

doi:10.1016/j.bbcan.2011.04.003

Cited by 48 publications

(75 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Altered expression levels of cancer-associated miRNAs have been found in HNSCC (22). We have also identified aberrantly expressed miRNAs including miR-133a and their target genes in HNSCC (7,13,21).…”

Section: Discussionmentioning

confidence: 84%

Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma

et al. 2012

View full text Add to dashboard Cite

Abstract. Our expression signatures of human cancers including head and neck squamous cell carcinoma (HNSCC) demonstrated that downregulation of microRNA-133a (miR133a) were frequently observed in cancer cells. The restoration of miR-133a in cancer cells revealed that it functions as a tumor suppressor. In this study, we investigated the novel molecular targets of miR-133a in HNSCC cancer cells and its oncogenic function, especially as it contributes to cancer cell migration and invasion. The genome-wide gene expression analysis and bioinformatics study showed that actin-related protein 2/3 complex subunit 5 (ARPC5) is a candidate target of miR-133a. Furthermore, luciferase reporter assay demonstrated that ARPC5 is directly regulated by miR-133a. Silencing of ARPC5 revealed significant inhibition of cell migration and invasion in HNSCC cell lines, SAS, HSC3 and IMC-3. In HSC3 cells, restoration of miR-133a or silencing ARPC5 led to a reorganization of the actin cytoskeleton and a subsequent change in cell morphology to a round, bleb-like shape. The expression levels of ARPC5 were significantly higher in HNSCC tissues than in noncancer tissues. Immunohistochemistry showed that the levels of ARPC5 expression were significantly higher in invasive cancer cells. ARPC5 contributed to cancer cell migration and invasion in HNSCC and this gene was directly regulated by miR-133a. Our analysis of novel tumor-suppressive miR-133a-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis. IntroductionHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and about 500,000 cases occur every year (1). In spite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall five-year survival rate for patients with HNSCC is only 40-50% (2). The poor prognosis is caused by metastasis and recurrence of the cancer. A deeper understanding of these problems is important to achieve further improvements in treatment of the disease. microRNAs (miRNAs) are small non-coding RNAs 20-22 nucleotides in length. They are involved in crucial biological processes, including development, differentiation, apoptosis and proliferation through imperfect pairing with target messenger RNAs (mRNAs) of protein-coding genes and transcriptional or post-transcriptional regulation of their expression. Bioinformatic predictions indicate that miRNAs regulate more than 30% of the protein coding genes (3). Currently, 1527 human miRNAs are registered at miRBase release 18.0 [http:// microrna.sanger.ac.uk/]. miRNAs are aberrantly expressed in many human cancers and can function either as tumor suppressors or oncogenes (4). In cancer pathways, normal regulatory mechanisms are disrupted by aberrant expression of tumor suppressive or oncogenic miRNAs.Our recent studies demonstrated that downregulation of miR-133a occurred frequently in various cancers, including HNSCC (5-7). In fact, miR-133a appeared to function as a tumor suppressor. Restora...

show abstract

Section: Discussionmentioning

confidence: 84%

Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma

et al. 2012

View full text Add to dashboard Cite

show abstract

“…A possible molecular mechanism contributing to this effect might be ERBB2 targeting by miR-125a/b which has experimentally been demonstrated. In fact, a high level of ERBB2 expression was observed in HNSCC suggesting disruption of miRNA suppression of this gene (Babu et al, 2011). Down regulation of miR-133a/b was also reported.…”

Section: Functional Analysis Of Mirnas In Hnsccmentioning

confidence: 90%

“…Reduced expression of almost all members of let-7 family has been observed in HNSCC by several studies (Babu et al, 2011). For example, it is shown that exogenous expression of let-7a promotes laryngeal cancer cells dysfunction by modulating proliferation, inhibiting metastasis and inducing apoptosis (Long et al, 2009).…”

Section: Functional Analysis Of Mirnas In Hnsccmentioning

confidence: 99%

“…miRNAs modulate gene expression at posttranscriptional level, primarily through their partial complementarity with the coding region or 3' untranslated region (UTR) of target mRNAs. This then leads to translational repression and/or degradation, therefore, the regulation of gene expression (Babu et al, 2011). In rare cases, they may also promote translation (Lin et al, 2011).They are involved in essential biological activities such as cellular differentiation, proliferation, development, apoptosis and cell cycle regulation (Shiiba et al, 2010).…”

Section: Micrornas Expression Profiling In Hnsccmentioning

confidence: 99%

“…The relevance of miRNAs in cancer was suggested by the observed changes in expression patterns and recurrent amplification as well as deletion of miRNA genes in cancer (Shiiba et al, 2010;Chen et al, 2010). It has been shown that there are two types of cancer-related miRNAs: oncogenic or tumour suppressor miRNAs (Table 4) (Babu et al, 2011). miRNAs expression profiling has been performed by microarray analysis or qRT-PCR methods.…”

Section: Micrornas Expression Profiling In Hnsccmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Genetics and Biology of Head and Neck Squamous Cell Carcinoma: Implications for Diagnosis, Prognosis and Treatment

Ganci¹,

Sacconi²,

Manciocco³

et al. 2012

Head and Neck Cancer

View full text Add to dashboard Cite

A robust six‐miRNA prognostic signature for head and neck squamous cell carcinoma

Zhao

Cui

2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) remains a major health problem worldwide. We aimed to identify a robust microRNA (miRNA)‐based signature for predicting HNSCC prognosis. The miRNA expression profiles of HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. The TCGA HNSCC cohort was randomly divided into the discovery and validation cohort. A miRNA‐based prognostic signature was built up based on TGCA discovery cohort, and then further validated. The downstream targets of prognostic miRNAs were subjected to functional enrichment analyses. The role of miR‐1229‐3p, a prognosis‐related miRNA, in tumorigenesis of HNSCC was further evaluated. A total of 305 significantly differentially expressed miRNAs were found between HNSCC samples and normal tissues. A six‐miRNA prognostic signature was constructed, which exhibited a strong association with overall survival (OS) in the TCGA discovery cohort. In addition, these findings were successfully confirmed in TCGA validation cohort and our own independent cohort. The miRNA‐based signature was demonstrated as an independent prognostic indicator for HNSCC. A risk signature‐based nomogram model was constructed and showed good performance for predicting the OS for HNSCC. The functional analyses revealed that the downstream targets of these prognostic miRNAs were closely linked to cancer progression. Mechanistically, in vitro analysis revealed that miR‐1229‐3p played a tumor promoting role in HNSCC. In conclusion, our study has developed a robust miRNA‐based signature for predicting the prognosis of HNSCC with high accuracy, which will contribute to improve the therapeutic outcome.

show abstract

A miR-centric view of head and neck cancers

Cited by 48 publications

References 56 publications

Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma

Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma

Molecular Genetics and Biology of Head and Neck Squamous Cell Carcinoma: Implications for Diagnosis, Prognosis and Treatment

A robust six‐miRNA prognostic signature for head and neck squamous cell carcinoma

Contact Info

Product

Resources

About