LncRNA NEF inhibits migration and invasion of HPV-negative cervical squamous cell carcinoma by inhibiting TGF-β pathway

LncRNA NEF was a recently identified tumor suppressor lncRNA in hepatocellular carcinoma. Our study aimed to explore the role of NEF in cervical squamous cell carcinoma (CSCC) patients. In the present study, expression of NEF in tumor tissue (cervical biopsies for healthy control) and serum of human papillomaviruses (HPV)-negative and HPV-positive CSCC patients as well as healthy controls was detected by qRT-PCR. Diagnostic and prognostic values of NEF for CSCC were evaluated by ROC curve and survival curve analysis, respectively. NEF expression vector was transfected into CSCC cells and the effects on cell migration and invasion as well as TGF-beta 1 expression were investigated by Transwell migration assay, Transwell invasion assay, and Western blot, respectively. We found that expression of NEF in cervical tissues (tumor tissues for CSCC patients) and serum was significantly down-regulated in HPV-negative CSCC patients than in healthy controls and HPV positive patients, but no significant differences were found between healthy controls and HPV positive patients. Low serum levels of NEF distinguished HPV-negative CSCC patients from healthy controls and indicated poor survival. NEF overexpression inhibited the migration and invasion of HPV-negative but not HPV-positive CSCC cells. NEF overexpression down-regulated TGF-beta 1 in HPV-negative CSCC cells but not in HPV-positive CSCC cells. TGF-beta 1 treatment reduced the effects of NEF overexpression on cell migration and invasion. Therefore, we conclude that lncRNA NEF may inhibit the migration and invasion of HPV-negative cervical squamous cell carcinoma by inhibiting TGF-beta pathway.