MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway.
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.
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
Juan
J
Du
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
LiNa
L
Wang
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
ChenXi
C
Li
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
HuiLun
H
Yang
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
YuanBo
Y
Li
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
Haiyang
H
Hu
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China.
Hui
H
Li
Department of Obstetrics and Gynecology, Second Affiliated Hospital, Harbin Medical University, 246 Xuefu Rd, 150086, Harbin, China. viaac1973@163.com.
ZongFeng
Z
Zhang
D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000077156:Gefitinib; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D000077156:Gefitinib; D035683:MicroRNAs; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D058539:Phosphatidylinositol 3-Kinase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; C525709:MIR221, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494929:PTEN protein, human
Cervical cancer; Gefitinib; PTEN; miR-221