Exogenous regucalcin negatively regulates the progression of cervical adenocarcinoma

Oncol Lett. 2019 Jul;18(1):609-616. doi: 10.3892/ol.2019.10374. Epub 2019 May 20.

Abstract

Cervical adenocarcinoma (CA) is a type of cervical cancer, and in previous decades its incidence has steadily increased. The upregulation of regucalcin (RGN) in various tumor cell types inhibits the progression of cancer. To understand the role of RGN in CA, RGN expression in human cervical cancer compared with normal tissues was analyzed using The Cancer Genome Atlas database (TCGA). Subsequently, transfection of lentivirus-mediated RGN into HeLa cells was conducted to study its function in tumor proliferation and metastasis. The expression of RGN and proteins associated with the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (EMT) were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell migration and invasion were evaluated using Transwell assays. Furthermore, cell proliferation, colony formation and cell cycle were assessed using the Cell Counting Kit-8, colony formation assay and flow cytometry, respectively. Lentivirus-mediated RGN effectively upregulated RGN expression, inhibited cell proliferation, retarded cellular invasion and promoted cell cycle arrest at the G2/M phase in HeLa cells. In addition, the expression levels of β-catenin, p-glycogen synthase kinase (GSK)-3β, matrix metalloproteinase (MMP)-3, MMP-7 and MMP-9 were effectively decreased, whilst those of E-cadherin and GSK-3β were increased. The results suggest that RGN may be an inhibitory factor in tumorigenesis, and its mechanism of inhibiting tumor proliferation and metastasis may be associated with Wnt/β-catenin signaling and EMT.

Keywords: HeLa; cervical cancer; gene therapy; lentivirus; regucalcin.