Exploration of the association between HIF3α mRNA and lncRNA MALAT1 in laryngeal squamous cell carcinoma by correlation analysis

Silva Garo Kyurkchiyan; Gergana Stancheva; Veronika Petkova; Yuliyan Hadzhiev; Venera Dobriyanova; Diana Popova; Radka Kaneva; Todor Miroslavov Popov

doi:10.3892/ol.2024.14425

Exploration of the association between HIF3α mRNA and lncRNA MALAT1 in laryngeal squamous cell carcinoma by correlation analysis

Oncol Lett. 2024 May 1;28(1):292. doi: 10.3892/ol.2024.14425. eCollection 2024 Jul.

Authors

Silva Garo Kyurkchiyan¹, Gergana Stancheva¹, Veronika Petkova¹, Yuliyan Hadzhiev², Venera Dobriyanova², Diana Popova², Radka Kaneva¹, Todor Miroslavov Popov²

Affiliations

¹ Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University, 1431 Sofia, Bulgaria.
² Department of Ear and Nose Treatment, UMHAT 'Tsaritsa Yoanna-ISUL', Medical University, 1537 Sofia, Bulgaria.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a significant global health burden, for which there has been limited evidence of improved survival rates. Although the roles of hypoxia-inducible factor (HIF)1α and HIF2α have been well documented in hypoxia, the involvement of HIF3α, particularly in LSCC, has been inadequately explored. The present study aimed to investigate the correlation between HIFα subunits and the hypoxia-related long noncoding RNAs (lncRNAs) MALAT1 and HOTAIR in 63 patients diagnosed with LSCC. Total RNA was extracted from fresh-frozen laryngeal tumor and adjacent normal tissues, and was subjected to reverse transcription-quantitative PCR for target detection. Statistical analyses were conducted using SPSS software, with significance set at P<0.05. The present study is the first, to the best of our knowledge, to report a positive moderate monotonic correlation (rs=0.347) and moderately strong positive linear correlation (r=0.630) between HIF3α mRNA and lncRNA MALAT1 in LSCC. Regression analysis revealed a direct association between 39.6% of both variables. Additionally, a positive correlation was observed between lncRNAs MALAT1 and HOTAIR (rs=0.353); HIF2α mRNA and lncRNA MALAT1 (rs=0.431); HIF3α mRNA and lncRNA HOTAIR (rs=0.279); and HIF3α mRNA and HIF2α mRNA (rs=0.285). Notably, a significant negative correlation (rs=-0.341) was detected between HIF3α mRNA and HIF1α mRNA, potentially indicative of the HIF switch or negative regulation. In addition, the present study investigated the association between HIFα subunits and the clinicopathological characteristics of patients. The results revealed a notable association between HIF1α transcript levels and the location of LSCC; specifically, subglottic tumors exhibited elevated HIF1α levels compared with glottic and supraglottic LSCC. Furthermore, a significant association was identified between HIF3α transcript levels and patient age (P=0.032) and positive family history (P=0.047). In conclusion, the present findings suggested a pivotal role for HIF3α in LSCC development, potentially involving direct regulation of lncRNA MALAT1. However, further research is warranted to elucidate its precise mechanisms.

Keywords: HIF1α; HIF2α; HIF3α; HOTAIR; MALAT1; correlation; expression; laryngeal cancer; laryngeal squamous cell carcinoma; long noncoding RNA.

Grants and funding

The present study was financed by the European Union-Next Generation EU, through the National Recovery and Resilience Plan of the Republic of Bulgaria (project no. BG-RRP-2.004-0004-C01, group 3.1.5).