Effect of miR-138 on migration and invasion of cervical cancer cells, and the underlying mechanism

Abstract

Purpose: To study the influence of microRNA-138 (miR-138) on the migration and invasion of cervical cancer cells, and the underlying mechanism. Methods: Fifteen cervical carcinoma subjects were enrolled in the study. Control group comprised cervical epithelial cell line (End1/E6E7)  while cervical cancer group was human cervical squamous cell carcinoma cell line c33a. Both were cultured routinely without any  treatment. In miR-138 overexpression group, cells were cultured in progeny of human cervical squamous carcinoma cell line c33a  infected with miR-138 gene overexpression lentivirus. Expression levels of miR-138 in excised cervical cancer tissues were determined  using qPCR. Cell proliferation was determined with CCK8 assay. Immunoblotting was utilized to assay protein expression levels.  Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine mRNA expression levels, while cell migration and  invasion were assessed by Transwell method. Results: There was significant down-regulation of miR-138 expression in cervical cancer  tissue, relative to nearby tissues (p < 0.05). In miR-138 overexpression group, cell proliferation, number of migrated and invaded cells  were significantly reduced, relative to corresponding levels in cervical cancer cells. There were significantly higher expression levels of  apoptosis-related proteins FAS, Bax and FasL in miR-138 overexpression group than in cervical cancer cells, while Bcl-2 was significantly  downregulated, relative to cervical cancer group (p < 0.05). In cervical cancer cells, mRNA and protein levels of SIRT1 and HIF-1α were  significantly up-regulated, relative to corresponding control, but levels of HIF1α and miR-138 were significantly reduced in overexpression  group when compared to cervical cancer group (p < 0.05). Conclusion: Up-regulating miR-138 in cervical cancer cells  reduces HIF-1α through inhibition of SIRT1 signaling, resulting in suppression of multiplication, migration and invasion of cervical cancer  cells, while enhancing apoptotic changes.