PMID- 35183226 OWN - NLM STAT- MEDLINE DCOM- 20220330 LR - 20220330 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 41 IP - 1 DP - 2022 Feb 19 TI - A reciprocal feedback between N6-methyladenosine reader YTHDF3 and lncRNA DICER1-AS1 promotes glycolysis of pancreatic cancer through inhibiting maturation of miR-5586-5p. PG - 69 LID - 10.1186/s13046-022-02285-6 [doi] LID - 69 AB - BACKGROUND: Glycolysis is a pivotal process in metabolic reprogramming of tumorigenesis. Previous research has indicated that lncRNAs might play crucial roles in glycolysis of various tumors. However, the function of lncRNAs in glycolysis of pancreatic cancer has not been fully elucidated. METHODS: Bio-information analyses were applied to reveal the potential glycolysis-associated lncRNA. RT-PCR and fluorescence in situ hybridization (FISH) assays were applied to detect the expression of antisense RNA1 of DICER1 (DICER1-AS1) in pancreatic cancer tissues and cell lines. Gain- and loss-of-function experiments were performed to evaluate the roles of DICER1-AS1 in glycolysis and tumorigenesis of PC. Mechanistic experiments including luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) were employed to uncover the downstream targets and regulatory mechanism of DICER1-AS1 in glycolysis of PC. RESULTS: Bio-information analysis indicated that DICER1-AS1 was downregulated in PC and negatively correlated with glycolytic genes expression. Meanwhile, overexpression of DICER1-AS1 inhibited glycolysis, proliferation, and metastasis of PC cells both in vitro and in vivo. Mechanistically, DICER1-AS1 promoted transcription of its sense gene DICER1 by recruiting transcriptional factor YY1 to the DICER1 promoter. Meanwhile, DICER1 promoted maturation of miR-5586-5p which consequently inhibited glycolytic gene expression including LDHA, HK2, PGK1, and SLC2A1. Notably, enhanced interaction between N6-methyladenosine (m6A) reader YTHDF3 and DICER1-AS1 led to degradation of DICER1-AS1 in response to glucose depletion. Moreover, our data revealed that YTHDF3 was a critical target for miR-5586-5p, by which forming a negative feedback with DICER1-AS1 to regulate glycolysis of PC. CONCLUSION: Our results implicate a negative feedback of m6A reader YTHDF3 and glycolytic lncRNA DICER1-AS1 is involved in glycolysis and tumorigenesis of PC. CI - (c) 2022. The Author(s). FAU - Hu, Yuhang AU - Hu Y AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Tang, Jiang AU - Tang J AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Xu, Fengyu AU - Xu F AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Chen, Jinhuang AU - Chen J AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Zeng, Zhu AU - Zeng Z AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Han, Shengbo AU - Han S AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Wang, Fan AU - Wang F AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Wang, Decai AU - Wang D AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Huang, Mengqi AU - Huang M AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Zhao, Yong AU - Zhao Y AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Huang, Yan AU - Huang Y AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Zhuo, Wenfeng AU - Zhuo W AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. FAU - Zhao, Gang AU - Zhao G AD - Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. gangzhao@hust.edu.cn. LA - eng GR - 81672406/National Natural Science Foundation of China/ GR - 81872030/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220219 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 RN - 0 (RNA, Long Noncoding) RN - 0 (RNA-Binding Proteins) RN - 0 (YTHDF3 protein, human) RN - CLE6G00625 (N-methyladenosine) RN - EC 3.1.26.3 (DICER1 protein, human) RN - EC 3.1.26.3 (Ribonuclease III) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) RN - K72T3FS567 (Adenosine) SB - IM MH - Adenosine/*analogs & derivatives/metabolism MH - Carcinogenesis MH - Cell Line, Tumor MH - Cell Proliferation MH - DEAD-box RNA Helicases/*metabolism MH - Glycolysis MH - Humans MH - Pancreatic Neoplasms/*genetics/pathology MH - RNA, Long Noncoding/*metabolism MH - RNA-Binding Proteins/*metabolism MH - Ribonuclease III/*metabolism MH - Transfection PMC - PMC8857805 OTO - NOTNLM OT - DICER1 OT - DICER1-AS1 OT - Glycolysis OT - LncRNA OT - Pancreatic cancer OT - YTHDF3 OT - m6A OT - miR-5586-5p COIS- The authors declare that they have no competing interest. EDAT- 2022/02/21 06:00 MHDA- 2022/03/31 06:00 PMCR- 2022/02/19 CRDT- 2022/02/20 20:26 PHST- 2021/09/27 00:00 [received] PHST- 2022/02/10 00:00 [accepted] PHST- 2022/02/20 20:26 [entrez] PHST- 2022/02/21 06:00 [pubmed] PHST- 2022/03/31 06:00 [medline] PHST- 2022/02/19 00:00 [pmc-release] AID - 10.1186/s13046-022-02285-6 [pii] AID - 2285 [pii] AID - 10.1186/s13046-022-02285-6 [doi] PST - epublish SO - J Exp Clin Cancer Res. 2022 Feb 19;41(1):69. doi: 10.1186/s13046-022-02285-6.