title: PFKL/miR-128 axis regulates glycolysis by inhibiting AKT phosphorylation and predicts poor survival in lung cancer.
abstract: MicroRNAs (miRNAs) affect cancer cell glucose metabolism by targeting mRNAs of diverse enzymes that have been implicated in oxidative phosphorylation (OXPHOS) and glycolytic pathways. However, the mechanisms that underlie miRNA-mediated regulation of phosphofructokinase (PFK), a key rate-limiting enzyme in glycolysis, remain largely unknown. Here, we show that miR-128 directly targets PFK liver type (PFKL) in lung cancer cells and regulates endogenous expression of PFKL at both the mRNA and protein levels. In line with this, overexpression of miR-128 decreased glucose uptake and lactate production, as well as increased cellular ATP content. Interestingly, knockdown of miR-128 was shown to promote lung cancer cell growth and colony formation. Moreover, we observed that miR-128 expression inversely correlated with PFKL mRNA levels in clinic lung cancer samples and that increased PFKL expression predicted poor overall survival in lung cancer patients. Mechanistically, we showed that miR-128 regulates PFKL via a feedback loop that involves inhibition of the AKT signaling pathway. Together, our results suggest that miR-128 acts as a metabolic regulator in lung cancer cells that may be therapeutically exploited.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ningbo University School of MedicineNingbo, ZJ 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineNingbo, ZJ 315211, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Ningbo University School of MedicineNingbo, ZJ 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineNingbo, ZJ 315211, China.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Ningbo University School of MedicineNingbo, ZJ 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineNingbo, ZJ 315211, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Le
authors.affiliation: Department of Chest Surgery, The Affiliated Hospital of Ningbo University School of Medicine Ningbo, ZJ 315020, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory, Ningbo No. 2 Hospital Ningbo, ZJ 315010, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Ningbo University School of MedicineNingbo, ZJ 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of MedicineNingbo, ZJ 315211, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Gong
keywords: glycolysis; lung cancer; microRNA; phosphofructokinase; phosphorylation