Dataset Information

Type I? phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer.

ABSTRACT: BACKGROUND:Emerging evidence suggests that metabolic alterations are a hallmark of cancer cells and contribute to tumor initiation and development. Cancer cells primarily utilize aerobic glycolysis (the Warburg effect) to produce energy and support anabolic growth. The type I? phosphatidylinositol phosphate kinase (PIPKI?) is profoundly implicated in tumorigenesis, however, little is known about its role in reprogrammed energy metabolism. METHODS:Loss- and gain-of-function studies were applied to determine the oncogenic roles of PIPKI? in colorectal cancer. Transcriptome analysis, real-time qPCR, immunohistochemical staining, Western blotting, and metabolic analysis were carried out to uncover the cellular mechanism of PIPKI?. FINDINGS:In this study, we showed that PIPKI? was frequently upregulated in colorectal cancer and predicted a poor prognosis. Genetic silencing of pan-PIPKI? suppressed cell proliferation and aerobic glycolysis of colorectal cancer. In contrast, the opposite effects were observed by overexpression of PIPKI?_i2. Importantly, PIPKI?-induced prolific effect was largely glycolysis-dependent. Mechanistically, PIPKI? facilitated activation of PI3K/Akt/mTOR signaling pathways to upregulate c-Myc and HIF1? levels, which regulate expression of glycolytic enzymes to enhance glycolysis. Moreover, pharmacological inhibition by PIPKI? activity with the specific inhibitor UNC3230 significantly inhibited colorectal cancer glycolysis and tumor growth. INTERPRETATION:Our findings reveal a new regulatory role of PIPKI? in Warburg effect and provide a key contributor in colorectal cancer metabolism with potential therapeutic potentials. FUND: National Key Research and Development Program of China, Outstanding Clinical Discipline Project of Shanghai Pudong, Natural Science Foundation of China, and Science and Technology Commission of Shanghai Municipality.

SUBMITTER: Peng W

PROVIDER: S-EPMC6604371 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Type Iγ phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer.

Peng Wei W Huang Wei W Ge Xiaoxiao X Xue Liqiong L Zhao Wei W Xue Junli J

EBioMedicine 20190516

<h4>Background</h4>Emerging evidence suggests that metabolic alterations are a hallmark of cancer cells and contribute to tumor initiation and development. Cancer cells primarily utilize aerobic glycolysis (the Warburg effect) to produce energy and support anabolic growth. The type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) is profoundly implicated in tumorigenesis, however, little is known about its role in reprogrammed energy metabolism.<h4>Methods</h4>Loss- and gain-of-function studies ...[more]

PMID: 31105034

Similar Datasets

Project description:ObjectiveCircular RNAs (circRNAs), pivotal in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), remain a significant point of investigation for potential therapeutic interventions. Our research was driven by the objective to decipher the roles and underlying mechanisms of hsa_circ_0044569 (circCOL1A1) in governing the malignant phenotypes and the Warburg effect in NPC.MethodsWe systematically collected samples from NPC tissues and normal nasopharyngeal epithelial counterparts. The expression levels of circCOL1A1, microRNA-370-5p (miR-370-5p), and prothymosin alpha (PTMA) were quantitatively determined using quantitative polymerase chain reaction (qPCR) and Western blotting. Transfections in NPC cell lines were conducted using small interfering RNAs (siRNAs) or vectors carrying the pcDNA 3.1 construct for overexpression studies. We interrogated the circCOL1A1/miR-370-5p/PTMA axis's role in cellular functions through a series of assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide for cell viability, colony formation for growth, Transwell assays for migration and invasion, and Western blotting for protein expression profiling. To elucidate the molecular interactions, we employed luciferase reporter assays and RNA immunoprecipitation techniques.ResultsOur investigations revealed that circCOL1A1 was a stable circRNA, highly expressed in both NPC tissues and derived cell lines. A correlation analysis with clinical pathological features demonstrated a significant association between circCOL1A1 expression, lymph node metastasis, and the tumor node metastasis staging system of NPC. Functionally, silencing circCOL1A1 led to substantial suppression of cell proliferation, migration, invasion, and metabolic alterations characteristic of the Warburg effect in NPC cells. At the molecular level, circCOL1A1 appeared to modulate PTMA expression by acting as a competitive endogenous RNA or 'sponge' for miR-370-5p, which in turn promoted the malignant characteristics of NPC cells.ConclusionTo conclude, our findings delineate that circCOL1A1 exerts its oncogenic influence in NPC through the modulation of the miR-370-5p/PTMA signaling axis.

Dataset Information

Type I? phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer.

Publications

Type Iγ phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets