Let7a suppresses cell proliferation via the TGFß/SMAD signaling pathway in cervical cancer.
Oncol Rep
; 36(6): 3275-3282, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27748903
ABSTRACT
Cervical cancer is the second most commonly diagnosed type of cancer among women after breast cancer. Recent research has addressed the role of microRNAs in cervical cancer. In the present study, we aimed to determine the effect of let7a on the regulation of the cell proliferation of cervical cancer and the related signaling pathway. Realtime RTPCR was used to detect the expression of let7a in the blood of cervical cancer patients and normal controls. The expression of let7a was also assessed in cervical cancer cell lines HeLa, SiHa and normal human immortalized keratinocyes HaCaT. Cell proliferation was tested by MTT assay, and cell apoptosis and cell cycle were examined by flow cytometric analysis in HeLa cells. Moreover, bioinformatic analysis, dualluciferase reporter assay and western blotting were used to confirm the target gene for let7a. In addition, the expression of TGFß1, SMAD4 and p53 were assessed by western blotting and realtime PCR. Our studies showed that the expression of let7a in cervical cancer was significantly reduced in cervical cancer patients compared with the expression in the normal control group. Cell proliferation of HeLa cells was inhibited by overexpression of let7a. The cell cycle analysis showed that an increased population was arrested in the G2 phase in the let7a mimic group when compared with that in the mimic control and untreated groups. In addition, the cell cyclerelated factor p53 was increased in the let7a overexpression group compared with that in the control and untreated groups. Furthermore, TGFBR1 was confirmed to be a target of let7a. Moreover, the expression of TGFß1 and SMAD4 proteins was elevated in cervical squamous carcinoma and cervical adenocarcinoma tissues. However, the expression of TGFß1 and SMAD4 was decreased in the let7aoverexpressing cervical cancer cell lines (HeLa, SiHa and CaSki). Our data suggest that let7a may play a role in the cell proliferation of cervical cancer by regulating the TGFß/SMAD pathway, and may participate in the regulation of the occurrence and development of cervical cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo do Útero
/
Proteínas Serina-Treonina Quinases
/
Receptores de Fatores de Crescimento Transformadores beta
/
MicroRNAs
/
Proliferação de Células
/
Proteína Smad4
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article