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.
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