MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway

Juan Du; LiNa Wang; ChenXi Li; HuiLun Yang; YuanBo Li; Haiyang Hu; Hui Li; ZongFeng Zhang

doi:10.1007/s13277-015-4247-8

MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway

Tumour Biol. 2016 Mar;37(3):3939-47. doi: 10.1007/s13277-015-4247-8. Epub 2015 Oct 19.

Authors

Juan Du¹, LiNa Wang¹, ChenXi Li¹, HuiLun Yang¹, YuanBo Li¹, Haiyang Hu¹, Hui Li¹, ZongFeng Zhang²

Affiliations

¹ Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
² Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China. [email protected].

PMID: 26482612
DOI: 10.1007/s13277-015-4247-8

Abstract

Patients with cervical cancer show minimal clinical response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). The molecular mechanisms underlying sensitivity to gefitinib are unknown. The purpose of this study was to investigate the possible mechanism by which microRNA-221 (miR-221) affects sensitivity to gefitinib. We showed that miR-221 expression was significantly increased in cervical cancer tissues compared with adjacent normal tissues. Upregulation of miR-221 expression in cervical cancer cells decreased PTEN expression levels, resulting in increased pAkt and BCL-2 expression. Importantly, gefitinib sensitivity was decreased by the upregulation of miR-221, which was blocked by pcDNA-PTEN co-transfection or by the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002. These data suggest that miR-221 can reduce the sensitivity of cervical cancer cells to gefitinib through the PTEN/PI3K/Akt signaling pathway. miR-221 represents a potential target to increase the sensitivity to gefitinib in cervical cancer treatment.

Keywords: Cervical cancer; Gefitinib; PTEN; miR-221.

MeSH terms

3' Untranslated Regions / genetics
Antineoplastic Agents / pharmacology
Blotting, Western
Cell Line, Tumor
Cell Survival / drug effects
Cell Survival / genetics
Chromones / pharmacology
Enzyme Inhibitors / pharmacology
Female
Gefitinib
HeLa Cells
Humans
MicroRNAs / genetics*
Morpholines / pharmacology
PTEN Phosphohydrolase / genetics*
PTEN Phosphohydrolase / metabolism
Phosphatidylinositol 3-Kinase / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Quinazolines / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Uterine Cervical Neoplasms / genetics*
Uterine Cervical Neoplasms / metabolism
Uterine Cervical Neoplasms / pathology

Substances

3' Untranslated Regions
Antineoplastic Agents
Chromones
Enzyme Inhibitors
MIRN221 microRNA, human
MicroRNAs
Morpholines
Phosphoinositide-3 Kinase Inhibitors
Proto-Oncogene Proteins c-bcl-2
Quinazolines
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase
PTEN protein, human
Gefitinib