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FBP2 inhibits sarcoma progression by restraining mitochondrial biogenesis

ABSTRACT: We show that expression of the gluconeogenic isozyme fructose-1,6-bisphosphatase 2 (FBP2) is silenced in a broad spectrum of soft tissue sarcoma (STS) subtypes, revealing an apparent common metabolic feature shared by diverse STS. Enforced FBP2 expression inhibits STS cell and tumor growth through two distinct mechanisms. First, cytosolic FBP2 antagonizes elevated glycolysis associated with the “Warburg effect”, thereby inhibiting sarcoma cell proliferation. Second, nuclear-localized FBP2 restrains mitochondrial biogenesis and respiration in a catalytic activity-independent manner by inhibiting the expression of nuclear respiratory factor (NRF1) and mitochondrial transcription factor A (TFAM). Specifically, nuclear FBP2 colocalizes with the c-Myc transcription factor at the TFAM locus and represses c-Myc-dependent TFAM expression. This unique dual function of FBP2 provides a rationale for its selective suppression in STS, identifying a potential metabolic vulnerability and possible therapeutic target. This study aims to globally compare the transcriptomes from control or FBP2-expressing LPS246 cells. Total RNA was isolated from 5 sets of control cells and 5 sets of FBP2-expressing cells using RNeasy Mini Kit (Qiagen). Low-throughput library prep using Illumina truSeq stranded mRNA kit. The sequencing were performed on Illumina Platform 100SR, with 312 million raw reads/sample.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137755 | GEO | 2019/09/20

REPOSITORIES: GEO

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