Relative quantitative expression of hypoxia-inducible factor-1α, −2α and −3α, and vascular endothelial growth factor A in laryngeal carcinoma

Abstract

Abstract. The aim of the present study was to determine the relative quantitative expression of hypoxia-inducible factor (HIF)-1α, -2α and -3α, and VEGF-A in laryngeal carcinoma. A total of 63 patients with carcinoma of the larynx were enrolled in the study. Total RNA was isolated from fresh, frozen normal and tumor tissues of each patient, and quantitative polymerase chain reaction was performed. HIF-1α was upregulated in the majority of patients (44 patients; 69.84%). By contrast, only 7 (11.11%) patients from the whole group displayed HIF-2α overexpression, while the HIF-3α isoform was silenced in the majority of patients (48 patients, 76.19%). A small group of 5 (7.94%) patients exhibited significant overexpression of the HIF-3α isoform. VEGF-A expression was significantly higher (P<0.05) in patients with upregulated HIF-1α (2.72±1.41 RQ) compared with patients without upregulated HIF-1α (1.86±1.46 RQ). There was a moderate positive correlation between mRNA expression levels of HIF-1α and VEGF-A (r s = 0.392; P<0.005). To the best of our knowledge, this study is first to report quantitative data with regard to the expression of all three HIF isoforms in malignant neoplasms. The findings suggest the existence of specific phenotypes of HIF expression in laryngeal carcinoma, where the HIF switch is absent.

HULC long noncoding RNA silencing suppresses angiogenesis by regulating ESM-1 via the PI3K/Akt/mTOR signaling pathway in human gliomas

“…Therefore, the PI3K/Akt/mTOR signaling pathway was the key component in the function of HULC in tumorigenesis via TGF-β1 activation. A hypoxic environment is a stimulus factor for tumor angiogenesis, and hypoxia inducing factor-1α (HIF-1α) is a key hypoxic response regulator that promotes the expression of VEGF-A, which is also a downstream component of the PI3K/Akt/mTOR signaling pathway [ 26 – 28 ]. We found that the expression of HIF-1α was reversed by HULC silencing, with higher expression being observed in a hypoxic environment, suggesting that HULC was also mediate angiogenesis by regulating the VEGF-A axis and the PI3K/Akt/mTOR signaling pathway in a hypoxic environment.…”

Correlation of HIF-1α, CXCR4 and MMP13 Expression in Laryngeal Squamous Cell Carcinoma With Cervical Nodal Status

“…This finding is inconsistent with previous studies that showed a positive correlation between HIF-1α and CXCR4 expression in many types of malignancy, and also in laryngeal SCC. 14,34 HIF-1α expression of laryngeal SCC tumor cells in this study tends to be low, while CXCR4 tends to be overexpressed. HIF-1α is known to be a major regulator for CXCR4 upregulation, hence a low expression of HIF-1α should be followed by low expression of CXCR4.…”

“…In this study, statistical analysis showed that there was a significant difference in HIF-1α expression in laryngeal SCC with nodal metastasis compared to laryngeal SCC without nodal metastasis (p<0,05 expression in laryngeal SCC. 13,14 and also in oral SCC. 15 Zhou et al in a meta-analysis study showed that HIF-1α associated with not only lymph node metastasis, but also tumor size, tumor stage and overall survival.…”

Serum hypoxia‐inducible factor‐2: A candidate prognostic biomarker for laryngeal cancer

“…However, Popov et al performed a comparative analysis of total mRNA levels of hypoxia-associated biomolecules in fresh normal and tumour tissue samples obtained from patients with LC. 31 They found that HIF-1 was upregulated in a significant majority (69.8%) of the study population, whereas overexpression of HIF-2 (11.1%) and HIF-3 (7.9%) was observed in a fewer number of patients. The authors emphasised that their findings indicated the opposite of 'HIF switch', even though they were unable to explain this contradiction.…”