2. Academic Validation
  3. Targeting oncogenic functions of miR-301a in head and neck squamous cell carcinoma by PI3K/PTEN and MEK/ERK pathways

Targeting oncogenic functions of miR-301a in head and neck squamous cell carcinoma by PI3K/PTEN and MEK/ERK pathways

  • Biomed Pharmacother. 2023 Mar 15;161:114512. doi: 10.1016/j.biopha.2023.114512.
Rocío Granda-Díaz 1,  Lorea Manterola 2,  Francisco Hermida-Prado 1,  René Rodríguez 3,  Laura Santos 4,  Vanessa García-de-la-Fuente 4,  María Teresa Fernández 5,  M Daniela Corte-Torres 6,  Juan P Rodrigo 1,  Saúl Álvarez-Teijeiro 7,  Charles H Lawrie 8,  Juana M Garcia-Pedrero 9
Affiliations

Affiliations

  • 1 Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain; Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
  • 2 Molecular Oncology group, Biodonostia Research Institute, San Sebastián, Spain.
  • 3 CIBERONC, Instituto de Salud Carlos III, Madrid, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain; Sarcomas and Experimental Therapies, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain.
  • 4 Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain; Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain.
  • 5 Histopathology Unit, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain.
  • 6 Biobank of Principado de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
  • 7 Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain; Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: saul.teijeiro@gmail.com.
  • 8 Molecular Oncology group, Biodonostia Research Institute, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Sino-Swiss Institute of Advanced Technology (SSIAT), Shanghai University, Shanghai, China. Electronic address: charles.lawrie@biodonostia.org.
  • 9 Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain; Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), University of Oviedo, Oviedo, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: juanagp.finba@gmail.com.
PMID: 36931033 DOI: 10.1016/j.biopha.2023.114512
Abstract

Treatment of head and neck squamous cell carcinomas (HNSCC), the sixth most frequent Cancer worldwide, remains challenging. miRNA dysregulation is closely linked to tumorigenesis and tumor progression, thus emerging as suitable targets for Cancer treatment. Transcriptomic analysis of TCGA HNSCC dataset revealed that miR-301a expression levels significantly increased in primary tumors, as compared to patient-matched normal tissue. This prompted us to investigate its pathobiological role and potential as new therapeutic target using different preclinical HNSCC models. miR-301a overexpression in HNSCC-derived cell lines led to enhanced proliferation and invasion, whereas miR-301 inhibition reduced these effects. In vivo validation was performed using an orthotopic mouse model. Results concordantly showed that the mitotic counts, the percentage of infiltration depth and Ki67 proliferative index were significantly augmented in the subgroup of mice harboring miR-301a-overexpressing tumors. Further mechanistic characterization revealed PI3K/PTEN/Akt and MEK/ERK pathways as central signaling nodes responsible for mediating the oncogenic activity of miR-301a observed in HNSCC cells. Notably, pharmacological disruption of PI3K and ERK signals with BYL-719 and PD98059, respectively, was effective to completely revert/abolish miR-301a-promoted tumor cell growth and invasion. Altogether, these findings demonstrate that miR-301a dysregulation plays an oncogenic role in HNSCC, thus emerging as a candidate therapeutic target for this disease. Importantly, available PI3K and ERK inhibitors emerge as promising anti-tumor agents to effectively target miR-301a-mediated signal circuit hampering growth-promoting and pro-invasive functions.

Keywords

ERK; Head and neck squamous cell carcinoma; PI3K; Signaling; Therapeutic target; miR-301a.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z