American Association for Cancer Research
10780432ccr172967-sup-190488_3_supp_4787060_p9gf8f.xls (147.5 kB)

Tale S3 from LncRNA–FEZF1-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling

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posted on 2023-03-31, 19:51 authored by Zehua Bian, Jiwei Zhang, Min Li, Yuyang Feng, Xue Wang, Jia Zhang, Surui Yao, Guoying Jin, Jun Du, Weifeng Han, Yuan Yin, Shenglin Huang, Bojian Fei, Jian Zou, Zhaohui Huang

Tale S3


Fudan University

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Fundamental Research Funds for the Central Universities

Medical Key Professionals Program of Jiangsu Province

Wuxi Medical Innovation Team

Key Medical Talents

Hospital Management Centre of Wuxi

National First-class Discipline Program of Food Science and Technology



Purpose: Long non-coding RNAs (lncRNAs) play key roles in human cancers. Here, FEZF1-AS1, a highly overexpressed lncRNA in colorectal cancer, was identified by lncRNA microarrays. We aimed to explore the roles and possible molecular mechanisms of FEZF1-AS1 in colorectal cancer.Experimental Design: LncRNA expression in colorectal cancer tissues was measured by lncRNA microarray and qRT-PCR. The functional roles of FEZF1-AS1 in colorectal cancer were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down, RNA immunoprecipitation and luciferase analyses were used to demonstrate the potential mechanisms of FEZF1-AS1.Results: We identified a series of differentially expressed lncRNAs in colorectal cancer using lncRNA microarrays, and revealed that FEZF1-AS1 is one of the most overexpressed. Further validation in two expanded colorectal cancer cohorts confirmed the upregulation of FEZF1-AS1 in colorectal cancer, and revealed that increased FEZF1-AS1 expression is associated with poor survival. Functional assays revealed that FEZF1-AS1 promotes colorectal cancer cell proliferation and metastasis. Mechanistically, FEZF1-AS1 could bind and increase the stability of the pyruvate kinase 2 (PKM2) protein, resulting in increased cytoplasmic and nuclear PKM2 levels. Increased cytoplasmic PKM2 promoted pyruvate kinase activity and lactate production (aerobic glycolysis), whereas FEZF1-AS1–induced nuclear PKM2 upregulation further activated STAT3 signaling. In addition, PKM2 was upregulated in colorectal cancer tissues and correlated with FEZF1-AS1 expression and patient survival.Conclusions: Together, these data provide mechanistic insights into the regulation of FEZF1-AS1 on both STAT3 signaling and glycolysis by binding PKM2 and increasing its stability. Clin Cancer Res; 24(19); 4808–19. ©2018 AACR.

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