Long noncoding RNA UCA1 promotes glutamine-driven anaplerosis of bladder cancer by interacting with hnRNP I/L to upregulate GPT2 expression

Zhao, Hua; Wu, Wenjing; Li, Xu; Chen, Wei

doi:10.1016/j.tranon.2022.101340

Cited by 14 publications

(11 citation statements)

References 42 publications

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“…1C). Although GPT2-mediated glutamate production has been shown to support cell proliferation in non-small cell lung cancer and breast cancer cell lines (19,20), it is the reverse reaction that produces -KG, which is important for cell proliferation in the majority of colorectal (21)(22)(23) and other cancers (24)(25)(26)(27)(28).…”

Section: Glutamine Feeds the Tca Cycle In An Mpc-dependent Mannermentioning

confidence: 99%

Mitochondrial pyruvate supports lymphoma proliferation by fueling a glutamate pyruvate transaminase 2–dependent glutaminolysis pathway

et al. 2022

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The fate of pyruvate is a defining feature in many cell types. One major fate is mitochondrial entry via the mitochondrial pyruvate carrier (MPC). We found that diffuse large B cell lymphomas (DLBCLs) consume mitochondrial pyruvate via glutamate-pyruvate transaminase 2 to enable α-ketoglutarate production as part of glutaminolysis. This led us to discover that glutamine exceeds pyruvate as a carbon source for the tricarboxylic acid cycle in DLBCLs. As a result, MPC inhibition led to decreased glutaminolysis in DLBCLs, opposite to previous observations in other cell types. We also found that MPC inhibition or genetic depletion decreased DLBCL proliferation in an extracellular matrix (ECM)–like environment and xenografts, but not in a suspension environment. Moreover, the metabolic profile of DLBCL cells in ECM is markedly different from cells in a suspension environment. Thus, we conclude that the synergistic consumption and assimilation of glutamine and pyruvate enables DLBCL proliferation in an extracellular environment-dependent manner.

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Section: Glutamine Feeds the Tca Cycle In An Mpc-dependent Mannermentioning

confidence: 99%

Mitochondrial pyruvate supports lymphoma proliferation by fueling a glutamate pyruvate transaminase 2–dependent glutaminolysis pathway

et al. 2022

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“…In the past decade, growing evidence has shown that lncRNAs play a vital role in gene expression and diverse biological processes by regulating transcription, sponging miRNAs, and modifying epigenetic regulation ( 6 , 7 ). Notably, enormous amounts of lncRNAs have been found to play an important role in invasion, metastasis and drug resistance in BC ( 8 – 10 ). For instance, lncRNA-SNHG1 promotes basal MIBC cell invasion by interacting with the PP2A catalytic subunit and inducing autophagy ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA HAGLROS Promotes the Malignant Progression of Bladder Cancer by Regulating the miR-330-5p/SPRR1B Axis

Xiao

Zuo

et al. 2022

Front. Oncol.

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Bladder cancer (BC) is the most common genitourinary malignancy worldwide, and its aetiology and pathogenesis remain unclear. Accumulating evidence has shown that HAGLROS is closely related to the occurrence and progression of various cancers. However, the biological functions and underlying mechanisms of HAGLROS in BC remain unknown. In the present study, the expression of HAGLROS in BC was determined by public dataset analysis, transcriptome sequencing analysis, qRT–PCR and ISH assays. Gain- or loss-of-function assays were performed to study the biological roles of HAGLROS in BC cells and nude mouse xenograft model. Bioinformatic analysis, qRT–PCR, western blot, immunohistochemistry, FISH assays, subcellular fractionation assays and luciferase reporter assays were performed to explore the underlying molecular mechanisms of HAGLROS in BC. Here, we found that HAGLROS expression is significantly upregulated in BC tissues and cells, and elevated HAGLROS expression was related to higher pathologic grade and advanced clinical stage, which is significant for BC diagnosis. HAGLROS can enhance the growth and metastasis of BC in vitro and in vivo. Furthermore, miR-330-5p downregulation reversed the BC cells proliferation, migration and invasion inhibited by silencing HAGLROS. SPRR1B silencing restored the malignant phenotypes of BC cells promoted by miR-330--5p inhibitor. Mechanistically, we found that HAGLROS functions as a microRNA sponge to positively regulate SPRR1B expression by sponging miR-330-5p. Together, these results demonstrate that HAGLROS plays an oncogenic role and may serve as a potential biomarker for the diagnosis and treatment of BC.

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“…In addition to lactate, other substrates, including glutamine, are known to fuel the TCA cycle and participate in energy production when coupled with oxidative phosphorylations [ 50 , 51 , 52 ]. By interacting with heterogeneous nuclear ribonucleoprotein (hnRNP) I/L to upregulate glutamate pyruvate transaminase (GPT2) expression, long non-coding RNA urothelial cancer associated 1 (UCA1) has recently been demonstrated to promote glutamine-driven anaplerosis in bladder cancer [ 53 ].…”

Section: Roles Of Mitochondria In Ucmentioning

confidence: 99%

Updates on the Pivotal Roles of Mitochondria in Urothelial Carcinoma

et al. 2022

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Mitochondria are important organelles responsible for energy production, redox homeostasis, oncogenic signaling, cell death, and apoptosis. Deregulated mitochondrial metabolism and biogenesis are often observed during cancer development and progression. Reports have described the crucial roles of mitochondria in urothelial carcinoma (UC), which is a major global health challenge. This review focuses on research advances in the role of mitochondria in UC. Here, we discuss the pathogenic roles of mitochondria in UC and update the mitochondria-targeted therapies. We aim to offer a better understanding of the mitochondria-modulated pathogenesis of UC and hope that this review will allow the development of novel mitochondria-targeted therapies.

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Long noncoding RNA UCA1 promotes glutamine-driven anaplerosis of bladder cancer by interacting with hnRNP I/L to upregulate GPT2 expression

Cited by 14 publications

References 42 publications

Mitochondrial pyruvate supports lymphoma proliferation by fueling a glutamate pyruvate transaminase 2–dependent glutaminolysis pathway

Mitochondrial pyruvate supports lymphoma proliferation by fueling a glutamate pyruvate transaminase 2–dependent glutaminolysis pathway

Long Noncoding RNA HAGLROS Promotes the Malignant Progression of Bladder Cancer by Regulating the miR-330-5p/SPRR1B Axis

Updates on the Pivotal Roles of Mitochondria in Urothelial Carcinoma

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