N6-methyladenosine Modification of Circ_0003215 Suppresses the Pentose Phosphate Pathway and Malignancy of Colorectal Cancer Through the MiR-663b/DLG4/G6PD Axis

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Sep 20

PMID 36127319

Authors

Baoxiang Chen

Yuntian Hong

Rui Gui

Huabin Zheng

Shunhua Tian

Xiang Zhai

Xiaoyu Xie

Quanjiao Chen

Qun Qian

Xianghai Ren

Lifang Fan

Congqing Jiang

Affiliations

Soon will be listed here.

Abstract

Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ_0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ_0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ_0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ_0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ_0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis.

Citing Articles

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