Let-7a suppresses cell proliferation via the TGF-β/SMAD signaling pathway in cervical cancer

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 let‑7a on the regulation of the cell proliferation of cervical cancer and the related signaling pathway. Real‑time RT‑PCR was used to detect the expression of let‑7a in the blood of cervical cancer patients and normal controls. The expression of let‑7a 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, dual‑luciferase reporter assay and western blotting were used to confirm the target gene for let‑7a. In addition, the expression of TGF‑β1, SMAD4 and p53 were assessed by western blotting and real‑time PCR. Our studies showed that the expression of let‑7a 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 let‑7a. The cell cycle analysis showed that an increased population was arrested in the G2 phase in the let‑7a mimic group when compared with that in the mimic control and untreated groups. In addition, the cell cycle‑related factor p53 was increased in the let‑7a overexpression group compared with that in the control and untreated groups. Furthermore, TGFBR1 was confirmed to be a target of let‑7a. Moreover, the expression of TGF‑β1 and SMAD4 proteins was elevated in cervical squamous carcinoma and cervical adenocarcinoma tissues. However, the expression of TGF‑β1 and SMAD4 was decreased in the let‑7a‑overexpressing cervical cancer cell lines (HeLa, SiHa and CaSki). Our data suggest that let‑7a may play a role in the cell proliferation of cervical cancer by regulating the TGF‑β/SMAD pathway, and may participate in the regulation of the occurrence and development of cervical cancer.

MicroRNAs in gynecological cancers: Small molecules with big implications

“…In HeLa and SiHa CC cells, smad7 is a target of miR-519d, an oncogenic miRNA that promotes metastasis [222]. Tumor suppressor let-7a targets smad4 to suppress TGF-β-mediated proliferation of CC cells [223]. In EC cells, smad3 is targeted by miR-23a to modulate TGF-β-mediated EMT [224].…”

Circulating MicroRNA-19b Identified From Osteoporotic Vertebral Compression Fracture Patients Increases Bone Formation

“…Plenty of studies have pointed to the involvement of miRNAs in various diseases, including cancer, (3)(4)(5)(6) heart diseases, (7,8) lung diseases, (9,10) nervous system disorders, (11,12) and even genetic diseases. (13)(14)(15) MicroRNAs can be transported in the extracellular circulation in several ways, including: (1) complexed with highdensity lipoproteins (HDL) or the Ago2 protein; (16) (2) encapsulated within microvesicles; (17) (3) accumulated in apoptotic bodies; (18) and (4) packaged within exosomes.…”

ssc‐miR‐204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2

“…Genetic variations in adipose tissue and variations in hormone secretion can cause many metabolic phenotypes, including T2D, 2 cardiovascular diseases 3 and obesity. 9 In addition, Wu et al 10 revealed that let-7a suppresses cell proliferation by targeting TGFBR1 in cervical cancer, 10 and Li et al 11 found that miR-9-5p facilitates cell growth and development by attenuating TGFBR2 in non-small-cell lung cancer. 7 The transforming growth factor-β (TGF-β) family contains three isoforms, TGF-β1, TGF-β2, and TGF-β3.…”