PMID- 33571038 OWN - NLM STAT- MEDLINE DCOM- 20220516 LR - 20220531 IS - 1557-8852 (Electronic) IS - 1084-9785 (Linking) VI - 37 IP - 4 DP - 2022 May TI - E2F1-Induced FTH1P3 Promoted Cell Viability and Glycolysis Through miR-377-3p/LDHA Axis in Laryngeal Squamous Cell Carcinoma. PG - 276-286 LID - 10.1089/cbr.2020.4266 [doi] AB - 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. FAU - Zhao, Lina AU - Zhao L AD - Department of Otolaryngology-Head and Neck Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou City, China. FAU - Zheng, Yi AU - Zheng Y AD - Department of Otolaryngology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou City, China. FAU - Zhang, Lei AU - Zhang L AD - Department of Otolaryngology-Head and Neck Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou City, China. FAU - Su, Lizhong AU - Su L AD - Department of Otolaryngology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou City, China. LA - eng PT - Journal Article DEP - 20210210 PL - United States TA - Cancer Biother Radiopharm JT - Cancer biotherapy & radiopharmaceuticals JID - 9605408 RN - 0 (E2F1 Transcription Factor) RN - 0 (E2F1 protein, human) RN - 0 (MIRN377 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (long non coding RNA FTH1P3, human) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.1.1.27 (LDHA protein, human) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Cell Survival MH - *E2F1 Transcription Factor/genetics MH - Gene Expression Regulation, Neoplastic MH - Glycolysis MH - Humans MH - *L-Lactate Dehydrogenase/genetics MH - *Laryngeal Neoplasms/genetics/pathology MH - *MicroRNAs/genetics MH - *RNA, Long Noncoding/genetics MH - *Squamous Cell Carcinoma of Head and Neck/genetics/pathology OTO - NOTNLM OT - E2F1 OT - FTH1P3 OT - LDHA OT - glycolysis OT - laryngeal squamous cell carcinoma OT - miR-377-3p EDAT- 2021/02/12 06:00 MHDA- 2022/05/17 06:00 CRDT- 2021/02/11 17:12 PHST- 2021/02/12 06:00 [pubmed] PHST- 2022/05/17 06:00 [medline] PHST- 2021/02/11 17:12 [entrez] AID - 10.1089/cbr.2020.4266 [doi] PST - ppublish SO - Cancer Biother Radiopharm. 2022 May;37(4):276-286. doi: 10.1089/cbr.2020.4266. Epub 2021 Feb 10.