Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1α axis

Hua, Qian; Mi, Baoming; Xu, Fei; Wen, Jun; Zhao, Li; Li, Jianjun; Huang, Gang

doi:10.7150/thno.43839

Cited by 183 publications

(136 citation statements)

References 40 publications

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“…Numerous studies revealed that lncRNAs interacted with protein and regulated its stability. For instance, hypoxia-induced lncRNA-AC020978 directly interacted with pyruvate kinase M2 (PKM2) and enhanced the protein stability of PKM2, promoting the proliferation and glycolysis of non-small cell lung cancer cells 51 . A previous study also showed that lncRNA-CF129 induced ubiquitination-dependent p53 degradation by enhancing the interaction between p53 and makorin ring finger protein 1 in PC 52 .…”

Section: Discussionmentioning

confidence: 99%

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer

Wang

et al. 2020

Theranostics

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Rationale: Previous studies have reported on the role of extracellular acidity in the metastasis of numerous cancers. However, the involvement of long noncoding RNA (lncRNA) in the extracellular acidity-induced cancer metastasis of pancreatic cancer (PC) remains unclear. Methods: Different expression levels of lncRNAs in PC cells under normal and acidic conditions were compared by RNA sequencing (RNA-seq). The effects of antisense lncRNA of metastasis suppressor 1 (MTSS1-AS) on acidic PC cells were assessed by gain- and loss-of-function experiments. Fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down, Western blot, luciferase reporter, and Chromatin immunoprecipitation assays were employed to determine the regulatory mechanisms of MTSS1-AS in the acidity-induced metastasis of PC cells. The expression of MTSS1-AS and associated pathways were compared in PC samples and peritumoral normal tissues. Results: RNA-seq demonstrated that MTSS1-AS was significantly downregulated in pancreatic cells cultured with the acidic medium. The overexpression of MTSS1-AS remarkably inhibited the acidity-promoted metastasis of PC cells by upregulating the expression of its sense gene metastasis suppressor 1 (MTSS1). Mechanistically, MTSS1-AS scaffolded the interaction between E3 ubiquitin-protein ligase STIP1 homology and U-box containing protein 1 (STUB1) and transcription regulator myeloid zinc finger 1 (MZF1), leading to ubiquitination-mediated degradation of MZF1. Further, MZF1 inhibited the expression of MTSS1 by binding to the MTSS1 promoter. Thus, the acidity-reduced MTSS1-AS facilitated the stability of MZF1 and its inhibitory effect on MTSS1 transcription, thereby promoting the metastasis of PC cells under acidic conditions. Moreover, MTSS1-AS was transcriptionally repressed by the binding of MYC proto-oncogene (Myc) with initiator (Inr) elements of the MTSS1-AS promoter. Meanwhile, MTSS1-AS mutually repressed the expression of Myc by impairing the MZF1-mediated transcription activation of Myc, thereby forming a negative feedback loop between MTSS1-AS and Myc in acidic PC cells. In accordance with the experimental results, MTSS1-AS and MTSS1 were downregulated in PC and correlated with poor overall survival. Conclusions: The results implicated that a reciprocal feedback loop between Myc and MTSS1-AS contributed to the extracellular acidity-promoted metastasis of PC, and indicated that MTSS1-AS was a valuable biomarker and therapeutic target for PC.

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Section: Discussionmentioning

confidence: 99%

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer

Wang

et al. 2020

Theranostics

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“…3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used for MTT assay as previously description 41 , 42 . Briefly, 500 cells were plated into each well of 6-well plate.…”

Section: Methodsmentioning

confidence: 99%

Functional roles of antisense enhancer RNA for promoting prostate cancer progression

et al. 2021

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“…PKM2 catalyses the conversion of phosphoenolpyruvate to pyruvate and generates ATP in the rate-limiting step in glycolysis, which switches glucose metabolism from the normal respiratory chain to lactate production in tumor cells [38,39]. Coincidentally, PKM2 activity is also regulated by posttranslational modifications, including O-GlcNAcylation, acetylation, phosphorylation, ubiquitination, etc [40][41][42][43][44][45]. The lncRNAs AC020978, Fez family zinc finger protein 1 antisense ribonucleic acid 1 (FEZF1-AS1), and LINC01554 can reprogram tumor metabolism by regulating the stability of PKM2 via the ubiquitin-mediated proteasome pathway.…”

Section: Pyruvate Kinase Muscle Isozyme M2 (Pkm2)mentioning

confidence: 99%

LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer

Tan

Lin

et al. 2020

Cancer Communications

421

223

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Altered metabolism is a hallmark of cancer, and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors. It is well recognized that long noncoding RNAs (lncRNAs) regulate energy metabolism in cancer. However, lncRNA-mediated posttranslational modifications and metabolic reprogramming are unclear at present. In this review, we summarized the current understanding of the interactions between the alterations in cancer-associated energy metabolism and the lncRNA-mediated posttranslational modifications of metabolic enzymes, transcription factors, and other proteins involved in metabolic pathways. In addition, we discuss the mechanisms through which these interactions contribute to tumor initiation and progression, and the key roles and clinical significance of functional lncRNAs. We believe that an in-depth understanding of lncRNA-mediated cancer metabolic

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Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1α axis

Cited by 183 publications

References 40 publications

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer

Functional roles of antisense enhancer RNA for promoting prostate cancer progression

LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer

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