Introduction: Hypoxia-inducible factor 1α (HIF-1α) regulates the transcription of many genes involved in key aspects of cancer biology. The aim of our study was to explore the effects of HIF-1α on the biological characteristics of the uterine cervix cancer (UCC) cell line SiHa, such as proliferation, apoptosis, and migration under normoxia and hypoxia.
Methods: Full-length HIF-1α (fL HIF-1α) and dominant-negative HIF-1α (dn HIF-1α) were transfected into UCC SiHa cells. The expression of HIF-1α and its targets such as vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), and human growth and transformation-dependent protein (HGTD-P) was detected by immunocytochemistry, Western blot, and semiquantitative reverse transcription-polymerase chain reaction. Cell proliferation, apoptosis, and migration were surveyed by methyl thiazolyl tetrazolium assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining, and scratching test.
Results: The expression of HIF-1α increased in fL HIF-1α but not in dn HIF-1α SiHa cells. Consistently, the expression of HIF-1α target genes such as VEGF, CXCR 4 , and HGTD-P increased in fL HIF-1α-transfected SiHa cells but decreased in dn HIF-1α-transfected SiHa cells. The UCC cells transfected with fL HIF-1α had increased cellular proliferation and migration. However, the inhibition of HIF-1α through dn HIF-1α attenuated cell proliferation and migration under both normoxia and hypoxia.
Conclusions: Hypoxia-inducible factor 1α affects the proliferation, apoptosis, and migration of UCC SiHa cells in part by regulating the expression of its target genes such as VEGF, HGTD-P, and CXCR4 . Targeting HIF-1α may be a promising strategy for molecular therapy for UCC.
- Hypoxia inducible factor 1α
- Uterine cervix cancer cell SiHa
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B. Tang and Y. Qu equally contributed to this work.
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