The LncRNA FEZF1-AS1 promotes tumor proliferation in colon cancer by regulating the mitochondrial protein PCK2.

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 in vitro. 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 in vitro and in vivo. 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.

In silico analysis for structure, function and T-cell epitopes of a hypothetical conserved (HP-C) protein coded by PVX_092425 in Plasmodium vivax.

OBJECTIVE: Plasmodium spp. merozoite glycosylphosphatidylinositol-anchored proteins (GPI-APs) considered as protective immunogen in novel vaccines against malaria. To analyze the structure and function of a hypothetical conserved (HP-C) GPI-AP coded by gene PVX_092425 from Plasmodium vivax, and find its potential T-cell epitopes for further vivax malaria vaccine study. METHODS: The structure, function and T-cell epitopes of the HP-C protein named Pvx_092425 were analyzed and predicted by online and offline bioinformatics software. RESULTS: The bioinformatics data showed that the Pvx_092425 is an 830 amino acid (AA) long polypeptide encoded by five exons gene PVX_092425.It contains a pectin lyase-like superfamily, an AA repeats region, a cys-rich region and a transmembrane domain (TM) in C-terminal region. The alignment analysis drew it has a unique AA repeats region among Plasmodium spp. It was located in the cytoplasm, secretory system or cellular nucleus of P. vivax merozoite. For the sequence, the fragment of I823-V829 inserts in the interior side of the membrane, and M1--A812 belongs to the cytoplasmic tail. It has seven protein-protein binding sites. The peptides with the best predicted binding affinities were human leucocyte antigen (HLA) HLA-A*0203, HLA-DRB1*0101 and HLA- DRB1*0701.Among these predicted peptides, 582FLWDKALFD590 epitope interacted with HLA-DRB1*0101 allele showed best binding affinity compared to others. Structural analysis explained that the epitope fits well into the epitope-binding groove of HLA-DRB1*0101. CONCLUSIONS: It proposes that the Pvx_092425 plays a key role during erythrocyte stage and generates information that is useful for development of blood-stage vaccine to block the merozoites invasion.