Abstract

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.

Details

Title
Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway
Author
Yang, Jin 1 ; Shi Xueke 1 ; Yang, Miao 1 ; Luo Jingjing 1 ; Gao Qinghong 2 ; Wang, Xiangjian 3 ; Wu, Yang 4 ; Tian Yuan 1 ; Wu Fanglong 1 ; Zhou, Hongmei 1 

 Sichuan University, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Center of Stomatology, West China Hospital of Stomatology, Chengdu, China (GRID:grid.13291.38) (ISNI:0000 0001 0807 1581) 
 Sichuan University, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Chengdu, China (GRID:grid.13291.38) (ISNI:0000 0001 0807 1581) 
 Sichuan University, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Center of Stomatology, West China Hospital of Stomatology, Chengdu, China (GRID:grid.13291.38) (ISNI:0000 0001 0807 1581); Zhejiang University, Department of Oral Medicine, the Second Affiliated Hospital, School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
 Sichuan University, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Center of Stomatology, West China Hospital of Stomatology, Chengdu, China (GRID:grid.13291.38) (ISNI:0000 0001 0807 1581); Zhejiang University, Department of General Dentistry, the Second Affiliated Hospital, School of Medicine, Hangzhou, China (GRID:grid.13402.34) (ISNI:0000 0004 1759 700X) 
Publication year
2021
Publication date
2021
Publisher
Springer Nature B.V.
ISSN
16742818
e-ISSN
20493169
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2504629047
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.