@Article{or.2022.03553,
AUTHOR = {HUAMIN WANG, YANTING WU, ZHENLEI WANG, YUHANG CHEN, JINYU MO, WEN GUAN, YALI ZHANG, HONGLIANG YAO},
TITLE = {The LncRNA FEZF1-AS1 promotes tumor proliferation in colon cancer by regulating the mitochondrial protein PCK2},
JOURNAL = {Oncology Research},
VOLUME = {29},
YEAR = {2021},
NUMBER = {3},
PAGES = {201--215},
URL = {http://www.techscience.com/or/v29n3/49188},
ISSN = {1555-3906},
ABSTRACT = {LncRNAs and metabolism represents two factors involved in cancer initiation and progression. However, the
interaction between lncRNAs and metabolism remains to be fully explored. In this study, lncRNA FEZF1-AS1 (FEZF1-
AS1) was found upregulated in colon cancer after screening all the lncRNAs of colon cancer tissues deposited in TCGA,
the result of which was further confirmed by RNAscope staining on a colon tissue chip. The results obtained using FEZF1-
AS1 knockout colon cancer cells (SW480 KO and HCT-116 KO) constructed using CRISPR/Cas9 system confirmed the
proliferation, invasion, and migration-promoting function of FEZF1-AS1 <i>in vitro</i>. Mechanistically, FEZF1-AS1 associated
with the mitochondrial protein phosphoenolpyruvate carboxykinase (PCK2), which plays an essential role in regulating
energy metabolism in the mitochondria. Knockdown of FEZF1-AS1 greatly decreased PCK2 protein levels, broke the
homeostasis of energy metabolism in the mitochondria, and inhibited proliferation, invasion, and migration of SW480
and HCT-116 cells. PCK2 overexpression in FEZF1-AS1 knockout cells partially rescued the tumor inhibitory effect
on colon cancer cells both <i>in vitro</i> and <i>in vivo</i>. Moreover, PCK2 overexpression specifically rescued the abnormal
accumulation of Flavin mononucleotide (FMN) and succinate, both of which play an important role in oxidative
phosphorylation (OXPHOS). Overall, these results indicate that FEZF1-AS1 is an oncogene through regulating energy
metabolism of the cell. This research reveals a new mechanism for lncRNAs to regulate colon cancer and provides a
potential target for colon cancer diagnosis and treatment.},
DOI = {10.32604/or.2022.03553}
}