Down-regulation of microRNA-146a is associated with high-risk human papillomavirus infection and epidermal growth factor receptor overexpression in penile squamous cell carcinoma

Elektra Peta, Rocco Cappellesso, Giulia Masi, Alessandro Sinigaglia, Marta Trevisan, Angela Grassi, Barbara Di Camillo, Elisa Vassarotto, Ambrogio Fassina, Giorgio Palù, Luisa Barzon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Dysregulation of host microRNA expression has been involved in the development and progression of human papillomavirus (HPV)–related tumors. Analysis of miR-146a expression in a series of 59 penile squamous cell carcinomas (PSCCs) showed that its levels were lower in high-risk HPV-positive than in HPV-negative PSCCs and inversely correlated with expression of epidermal growth factor receptor (EGFR), a known target for miR-146a. Analysis of genotype distribution for rs2910164, a common functional polymorphism of miR-146a, did not identify correlations with miR-146a levels and EGFR expression in PSCCs. In vitro experiments demonstrated that E6 of HPV type 16, but not low-risk HPV-6, down-regulated miR-146a in human foreskin keratinocytes and up-regulated EGFR. Ectopic expression of miR-146a decreased expression of EGFR and inhibited proliferation of keratinocytes and cervical carcinoma cells. EGFR is commonly overexpressed in penile cancer and in other squamous cell carcinomas. Molecular mechanisms leading to EGFR overexpression and activation are known for HPV-negative cancers and include amplification or mutations of the EGFR gene. The results of this study indicate that down-regulation of miR-146a may represent another mechanism of EGFR overexpression in PSCCs, which can be mediated by high-risk HPV E6 in HPV-related tumors.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalHuman Pathology
Volume61
Early online dateNov 4 2016
DOIs
Publication statusPublished - Mar 1 2017

Fingerprint

Papillomavirus Infections
MicroRNAs
Epidermal Growth Factor Receptor
Squamous Cell Carcinoma
Down-Regulation
Keratinocytes
Penile Neoplasms
Human papillomavirus 6
erbB-1 Genes
Foreskin
Neoplasms
Human papillomavirus 16
Human Development
Genotype
Carcinoma
Mutation

Keywords

  • E6
  • Epidermal growth factor receptor
  • HPV-16
  • Human papillomavirus
  • MiR-146a
  • Penile squamous cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Down-regulation of microRNA-146a is associated with high-risk human papillomavirus infection and epidermal growth factor receptor overexpression in penile squamous cell carcinoma. / Peta, Elektra; Cappellesso, Rocco; Masi, Giulia; Sinigaglia, Alessandro; Trevisan, Marta; Grassi, Angela; Di Camillo, Barbara; Vassarotto, Elisa; Fassina, Ambrogio; Palù, Giorgio; Barzon, Luisa.

In: Human Pathology, Vol. 61, 01.03.2017, p. 33-40.

Research output: Contribution to journalArticle

Peta, E, Cappellesso, R, Masi, G, Sinigaglia, A, Trevisan, M, Grassi, A, Di Camillo, B, Vassarotto, E, Fassina, A, Palù, G & Barzon, L 2017, 'Down-regulation of microRNA-146a is associated with high-risk human papillomavirus infection and epidermal growth factor receptor overexpression in penile squamous cell carcinoma', Human Pathology, vol. 61, pp. 33-40. https://doi.org/10.1016/j.humpath.2016.10.019
Peta, Elektra ; Cappellesso, Rocco ; Masi, Giulia ; Sinigaglia, Alessandro ; Trevisan, Marta ; Grassi, Angela ; Di Camillo, Barbara ; Vassarotto, Elisa ; Fassina, Ambrogio ; Palù, Giorgio ; Barzon, Luisa. / Down-regulation of microRNA-146a is associated with high-risk human papillomavirus infection and epidermal growth factor receptor overexpression in penile squamous cell carcinoma. In: Human Pathology. 2017 ; Vol. 61. pp. 33-40.
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