Long non-coding MIR205HG depletes Hsa-miR-590-3p leading to unrestrained proliferation in head and neck squamous cell carcinoma

Silvia Di Agostino, Fabio Valenti, Andrea Sacconi, Giulia Fontemaggi, Matteo Pallocca, Claudio Pulito, Federica Ganci, Paola Muti, Sabrina Strano, Giovanni Blandino

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Over 70% of head & neck squamous cell carcinoma (HNSCC) patients carry TP53 oncogenic mutations. Here we studied the role of specific tumor-derived mutant p53 proteins in the aberrant transcription of long non-coding (lnc) MIR205HG gene in head and neck cancer cells. Methods: To understand the role of lncMIR205HG, that we showed to be transcriptionally regulated by mutant p53 in HNSCC, we have employed siRNA and shRNA in CAL27 and FaDu HNSCC cell lines to suppress p53 gene expression in ChIP assays and RT-qPCR. We validated our findings in a cohort of 522 HNSCC patients from The Cancer Genome Atlas Data Portal (TCGA). We further evaluated our results in 63 HNSCC tumor samples collected at our institute, 32 of which were characterized by mutated TP53 (missense mutations) while 31 were characterized by wild-type TP53. Results: Maturation of pre-MIR205HG transcript produces two non-coding RNAs, lncMIR205HG and hsa-miR-205-5p. Down-regulation of lncMIR205HG expression significantly reduced cell proliferation, cell migration and clonogenic activity of head and neck cancer cells. Expression of MIR205HG was significantly increased in HNSCC with mutated TP53 when compared with matched non-tumoral tissues. Furthermore, MIR205HG expression levels were significantly higher in tumoral samples with mutant p53 than in tumoral tissues expressing wild-type p53. Mechanistically, MIR205HG depletes endogenous miR-590-3p leading to increased cyclin B, cdk1, and YAP protein expression. Conclusions: Taken together, these findings identify a transcriptional and post-transcriptional molecular network that includes mutant p53 protein, lncMIR205HG, YAP, and other proliferation-related genes, which are enriched in HNSCC patients with poor prognosis.

Original languageEnglish
Pages (from-to)1850-1868
Number of pages19
JournalTheranostics
Volume8
Issue number7
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Mutant Proteins
Head and Neck Neoplasms
Small Interfering RNA
Cyclin B
Neoplasms
Untranslated RNA
Atlases
Gene Regulatory Networks
p53 Genes
Missense Mutation
Genes
Cell Movement
Squamous Cell Carcinoma
Neck
Down-Regulation
Head
Cell Proliferation
Genome
Gene Expression
Cell Line

Keywords

  • Gene-expression
  • HNSCC
  • Mutant p53/YAP
  • Non-coding RNA
  • Proliferation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Long non-coding MIR205HG depletes Hsa-miR-590-3p leading to unrestrained proliferation in head and neck squamous cell carcinoma. / Agostino, Silvia Di; Valenti, Fabio; Sacconi, Andrea; Fontemaggi, Giulia; Pallocca, Matteo; Pulito, Claudio; Ganci, Federica; Muti, Paola; Strano, Sabrina; Blandino, Giovanni.

In: Theranostics, Vol. 8, No. 7, 01.01.2018, p. 1850-1868.

Research output: Contribution to journalArticle

Agostino, SD, Valenti, F, Sacconi, A, Fontemaggi, G, Pallocca, M, Pulito, C, Ganci, F, Muti, P, Strano, S & Blandino, G 2018, 'Long non-coding MIR205HG depletes Hsa-miR-590-3p leading to unrestrained proliferation in head and neck squamous cell carcinoma', Theranostics, vol. 8, no. 7, pp. 1850-1868. https://doi.org/10.7150/thno.22167
Agostino, Silvia Di ; Valenti, Fabio ; Sacconi, Andrea ; Fontemaggi, Giulia ; Pallocca, Matteo ; Pulito, Claudio ; Ganci, Federica ; Muti, Paola ; Strano, Sabrina ; Blandino, Giovanni. / Long non-coding MIR205HG depletes Hsa-miR-590-3p leading to unrestrained proliferation in head and neck squamous cell carcinoma. In: Theranostics. 2018 ; Vol. 8, No. 7. pp. 1850-1868.
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AU - Valenti, Fabio

AU - Sacconi, Andrea

AU - Fontemaggi, Giulia

AU - Pallocca, Matteo

AU - Pulito, Claudio

AU - Ganci, Federica

AU - Muti, Paola

AU - Strano, Sabrina

AU - Blandino, Giovanni

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AB - Over 70% of head & neck squamous cell carcinoma (HNSCC) patients carry TP53 oncogenic mutations. Here we studied the role of specific tumor-derived mutant p53 proteins in the aberrant transcription of long non-coding (lnc) MIR205HG gene in head and neck cancer cells. Methods: To understand the role of lncMIR205HG, that we showed to be transcriptionally regulated by mutant p53 in HNSCC, we have employed siRNA and shRNA in CAL27 and FaDu HNSCC cell lines to suppress p53 gene expression in ChIP assays and RT-qPCR. We validated our findings in a cohort of 522 HNSCC patients from The Cancer Genome Atlas Data Portal (TCGA). We further evaluated our results in 63 HNSCC tumor samples collected at our institute, 32 of which were characterized by mutated TP53 (missense mutations) while 31 were characterized by wild-type TP53. Results: Maturation of pre-MIR205HG transcript produces two non-coding RNAs, lncMIR205HG and hsa-miR-205-5p. Down-regulation of lncMIR205HG expression significantly reduced cell proliferation, cell migration and clonogenic activity of head and neck cancer cells. Expression of MIR205HG was significantly increased in HNSCC with mutated TP53 when compared with matched non-tumoral tissues. Furthermore, MIR205HG expression levels were significantly higher in tumoral samples with mutant p53 than in tumoral tissues expressing wild-type p53. Mechanistically, MIR205HG depletes endogenous miR-590-3p leading to increased cyclin B, cdk1, and YAP protein expression. Conclusions: Taken together, these findings identify a transcriptional and post-transcriptional molecular network that includes mutant p53 protein, lncMIR205HG, YAP, and other proliferation-related genes, which are enriched in HNSCC patients with poor prognosis.

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