E2F1-Induced FTH1P3 Promoted Cell Viability and Glycolysis Through miR-377-3p/LDHA Axis in Laryngeal Squamous Cell Carcinoma.

Abstract

Background: Laryngeal squamous cell carcinoma (LSCC) has poor prognosis, and the mechanism underlying the pathogenesis of LSCC remains unclear. Recently, a study has shown that long nonprotein coding RNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) plays a crucial role in tumor pathogenesis. This study explored the potential role of FTH1P3 in LSCC. Materials and Methods: The expression of E2F1 and FTH1P3 in LSCC was analyzed by quantitative real time-polymerase chain reaction assay. The direct targets of FTH1P3 and miR-377-3p were predicted, followed by functional validation. The functional role of FTH1P3 was investigated in AMC-HN-8 and TU686 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and the measurement of glucose uptake and L-lactate production. Results: The results showed that overexpression of FTH1P3 promoted cell viability and glycolysis in LSCC cells, but knockdown of FTH1P3 suppressed this behavior. Upregulated FTH1P3 was associated with increased E2F1 expression in LSCC patients. E2F1 was proved to induce FTH1P3 expression in LSCC cells. FTH1P3 modulated miR-377-3p expression by targeting miR-377-3p. Interestingly, LDHA was identified to be a target of miR-377-3p, and FTH1P3 promoted LDHA expression by suppressing miR-377-3p. In addition, knockdown of FTH1P3 mitigated E2F1-induced cell viability and glycolysis through miR-377-3p/LDHA in AMC-HN-8 cells. More importantly, knockdown of E2F1 inhibited tumor growth and FTH1P3 expression in vivo. Conclusion: In conclusion, these findings revealed that E2F1-induced FTH1P3 promoted cell viability and glycolysis through miR-377-3p/LDHA axis in LSCC, which could provide a promising novel strategy for LSCC treatment.

• Authors: Lina Zhao, Yi Zheng, Lei Zhang, Lizhong Su
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 37 Issue 4 Pg. 276-286 (May 2022) ISSN: 1557-8852 [Electronic] United States
• PMID: 33571038 (Publication Type: Journal Article)

Chemical References

• E2F1 Transcription Factor
• E2F1 protein, human
• MIRN377 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• long non coding RNA FTH1P3, human
• L-Lactate Dehydrogenase
• LDHA protein, human

Topics

• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cell Survival
• E2F1 Transcription Factor (genetics)
• Gene Expression Regulation, Neoplastic
• Glycolysis
• Humans
• L-Lactate Dehydrogenase (genetics)
• Laryngeal Neoplasms (genetics, pathology)
• MicroRNAs (genetics)
• RNA, Long Noncoding (genetics)
• Squamous Cell Carcinoma of Head and Neck (genetics, pathology)