miR-517a promotes Warburg effect in HCC by directly targeting FBP1

Abstract

PurposeHepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide. Our aim is to explore the expression and biological function of miR-517a in HCC.Materials and methodsWe performed qRT-PCR to detect the expression of miR-517a in clinical samples and cell lines. CKK-8 assay and colony formation assay were employed to detect the miR-517a regulated cell proliferation. Glucose uptake and lactate production were examined to determine the Warburg effect. We also performed ECAR assay using Seahorse system. Luciferase acitivy assay was used to examine the binding of FBP1 3′UTR by miR-517a.ResultsmiR-517a was upregulated in HCC samples in both genomic and mRNA levels. Moreover, overexpression of miR-517a promoted cell proliferation and Warburg effect. Mechanically, miR-517a could directly target the 3′-UTR of FBP1. In addition, restoring the expression of FBP1 inhibited cell growth.ConclusionWe demonstrated that miR-517a acts as an oncogene to promote Warburg effect in HCC, favoring tumor growth, and miR-517a/FBP1 could be a novel target for HCC treatment.

TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p

“…In this study, GSEA analysis showed that high expression of TOP2A was closely associated with cell cycle. Fluorescence activated Cell Sorting (FASC) showed that TOP2A knockdown could inhibit cell proliferation by inducing cell cycle arrest from G2 to M phase, which is consistent with previous reports 20 . In this pathway CDK1-Cyclin B1 complex plays an important role in promoting the G2/M phase transition.…”

“…Furthermore, miRNA is considered as oncogenes or tumor suppressor genes respectively 15 . For example, studies showed that miR-218 and miR-200 prevent the proliferation and metastasis of HCC cells whereas miR-330 and miR-517a promote the development of HCC 17 - 20 . Other studies reported that miR-144-3p functions as a key suppressor of HCC but the underlying mechanism is to be further identified 21 .…”

Mitochondrial Metabolic Signatures in Hepatocellular Carcinoma

“…Metabolic reprogramming, a key feature of which is the Warburg effect, is widely recognized as a major hallmark of cancer, including HCC [71,[85][86][87][88][89][90][91][92][93][94][95]. Several studies not only suggested that tumor cells depend on glycolysis as a primary energy source but also implicated mitochondrial dysfunction in the initiation and progression of HCC [85,[92][93][94].…”

“…Several miRNAs have been shown to play a potential role in glycolysis and to be associated with HCC progression. These include miR-199a-5p, miR-517a, miR-885-5p, miR-129-5p, and miR-3662 [87][88][89]96]. While miR-517a acts as an oncogene to promote glycolysis in HCC, miR-199a-5p and miR-885-5p suppress glucose consumption, lactate production, cell proliferation, and tumorigenesis in liver cancer cells by targeting HK2 [87,88,96].…”

“…These include miR-199a-5p, miR-517a, miR-885-5p, miR-129-5p, and miR-3662 [87][88][89]96]. While miR-517a acts as an oncogene to promote glycolysis in HCC, miR-199a-5p and miR-885-5p suppress glucose consumption, lactate production, cell proliferation, and tumorigenesis in liver cancer cells by targeting HK2 [87,88,96]. miR-3662 suppresses the Warburg effect and HCC progression by decreasing HIF-1α expression [89].…”