circHECTD1 facilitates glutaminolysis to promote gastric cancer progression by targeting miR-1256 and activating β-catenin/c-Myc signaling

Cell Death & Disease
Juan CaiXueliang Zuo

Abstract

Circular RNAs (circRNAs) have emerged as crucial regulators of human cancers. Glutaminolysis supplies cancer cells with adequate nitrogen and carbon to replenish the tricarboxylic acid cycle, contributing to the survival and progression of tumor cells. However, the association between circRNAs and glutaminolysis remains unclear. In this study, we showed that circHECTD1 expression was markedly upregulated in gastric cancer (GC) and was associated with lymph node metastasis and American Joint Committee on Cancer stage. The circHECTD1 expression level was found to be an independent prognostic factor for GC patients. circHECTD1 knockdown inhibited GC cell glutaminolysis, proliferation, migration, and invasion, whereas circHECTD1 overexpression promoted GC progression. Dual-luciferase and RNA immunoprecipitation assays demonstrated that miR-1256 was a direct downstream target of circHECTD1. circHECTD1 targeted miR-1256 and subsequently increased the expression level of USP5. The circHECTD1/miR-1256/USP5 axis exerted its tumor-promoting effects by activating the downstream β-catenin/c-Myc signaling pathway. In vivo mouse models further verified the oncogenic roles of circHECTD1 in GC. Our results revealed that circHECTD1 is a glutami...Continue Reading

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Citations

Dec 18, 2019·Molecular Genetics & Genomic Medicine·Xiaopeng CaiFang Yu
Jan 25, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xiu-Yan HuangZhao-You Tang
Jun 10, 2020·Cell Proliferation·Hui NieChunlin Ou
May 8, 2020·International Journal of Oncology·Hao-Ying WangYong-Ning Zhou
Jul 28, 2020·Cancers·Adenilson Leão PereiraAmanda Ferreira Vidal
Jun 5, 2020·Cellular Oncology (Dordrecht)·Arash PoursheikhaniSadegh Babashah
Apr 25, 2020·International Journal of Molecular Sciences·Yunuen Ortiz-PedrazaMarcela Lizano
Jan 9, 2021·Molecular and Cellular Biochemistry·Yang YangChangjun Yu
Feb 10, 2021·Journal of Cellular Physiology·Chenlong LiPeng Liang
Jan 6, 2021·Journal of Experimental & Clinical Cancer Research : CR·Jiacheng CaoZekuan Xu
Nov 8, 2020·Seminars in Cancer Biology·Rongfu TuGuoliang Qing
Jul 17, 2021·Cardiovascular Drugs and Therapy·Kai WangLu-Yu Zhou
Aug 28, 2021·Biomedicines·Ekaterina Mikhailovna StasevichAnton Markovich Schwartz
Oct 15, 2021·Journal of Medicinal Chemistry·Mandeep K MannMatthieu Schapira

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Datasets Mentioned

BETA
SGC7901
GES-1

Methods Mentioned

BETA
PCR
immunoprecipitation
xenograft
xenografts
RIP
transfection
Assay

Software Mentioned

CIRCexplorer2
CircInteractome
GraphPad Prism
CIRI2
Image Lab
TargetScan
SPSS
miRDB

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