miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer.

British Journal of Cancer
Giovannina BariscianoL Sabatino

Abstract

Metabolic reprogramming towards aerobic glycolysis in cancer supports unrestricted cell proliferation, survival and chemoresistance. The molecular bases of these processes are still undefined. Recent reports suggest crucial roles for microRNAs. Here, we provide new evidence of the implication of miR-27a in modulating colorectal cancer (CRC) metabolism and chemoresistance. A survey of miR-27a expression profile in TCGA-COAD dataset revealed that miR-27a-overexpressing CRCs are enriched in gene signatures of mitochondrial dysfunction, deregulated oxidative phosphorylation, mTOR activation and reduced chemosensitivity. The same pathways were analysed in cell lines in which we modified miR-27a levels. The response to chemotherapy was investigated in an independent cohort and cell lines. miR-27a upregulation in vitro associated with impaired oxidative phosphorylation, overall mitochondrial activities and slight influence on glycolysis. miR-27a hampered AMPK, enhanced mTOR signalling and acted in concert with oncogenes and tumour cell metabolic regulators to force an aerobic glycolytic metabolism supporting biomass production, unrestricted growth and chemoresistance. This latter association was confirmed in our cohort of patients and...Continue Reading

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Methods Mentioned

BETA
flow cytometry
Assay
xenograft
biopsies
xenografts
surgical resection
dissection

Software Mentioned

mirWalk
IPA
LEDGE analysis
FACSuite
TCPA
Leading - Edge analysis ( LEDGE )
Gene Set Enrichment Analysis ( GSEA )
Imagelab
JMP
Statistical Package from Social Science ( SPSS

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