Long non‐coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the <scp>mTOR</scp>–STAT3/microRNA143 pathway

Li, Zhengkun; Xu, Li; Wu, Shouzhen; Xue, Mei; Chen, Wei

doi:10.1111/cas.12461

Cited by 222 publications

(183 citation statements)

References 29 publications

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“…There was no significant difference for PKM2 mRNA in the breast cancer with miR-122-5p or the miRNA control transfection, but, PKM2 protein showed down-regulation in the cells. HK2 was regulated by miR-143 [24], miR-155 [25], miR-199a-5p [26], miR-29b [27,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43], miR-140-5p in various cancers like bladder cancer, liver cancer and prostate cancer. LDHA was regulated by miR-383, miR34a, miR-122, miR-30a-5p and other miRNAs in cancer.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

Xia¹,

Yu²,

Mao³

et al. 2018

Oncotarget

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Exosomes contain many important components including miRNAs for cancerstromal communication. Mesenchymal stromal cells support tumor development, however, the low expression of miRNAs in exosomes and their regulation roles from mesenchymal stromal cells are still unclear. In this study, we hypothesized that mesenchymal stromal cells-derived exosomes promote breast cancer cell glycolysis. Our results showed that mesenchymal stromal cells-derived exosomes promoted cell proliferation and glycolysis of breast cancer cells. Furthermore, sequencing of exosomal RNAs revealed miR-216b-5p, miR-33a-5p and miR-122-5p were lack of expression in exosomes from mesenchymal stromal cells. MiR-216b-5p, miR-33a-5p and miR-122-5p overexpression in breast cancer cells suppressed glycolysis by targeting HK2, LDHA and PKM2 respectively. These results provided valuable insights and mechanism of mesenchymal stromal cells-secreted exosomes on the glycolysis of breast cancer.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

Xia¹,

Yu²,

Mao³

et al. 2018

Oncotarget

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“…The Warburg effect is controlled by key glycolytic enzymes including hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) [8]. Lately, long non-coding RNAs have been identified as a class of crucial regulators of the Warburg effect [9,10]. However, the detailed lncRNA regulatory network modulated by 20(S)-Rg3 to prevent the Warburg effect in ovarian cancer cells has not been fully explored.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

Zheng

Zhou

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Warburg effect is one of the main metabolic features for cancers, with long non-coding RNA (lncRNA) being involved as a class of crucial regulators. Our previous studies have shown that ginsenoside 20(S)-Rg3, an active saponin monomer extracted from red ginseng, inhibits the Warburg effect in ovarian cancer cells. However, the detailed lncRNA regulatory network modulated by 20(S)-Rg3 to prevent the Warburg effect in ovarian cancer cells has not been explored. Methods: High-throughput sequencing was used to screen out the differentially expressed lncRNAs between 20(S)-Rg3-treated and non-treated SKOV3 cells. The levels of lncRNA H19 and miR-324-5p were manipulated in SKOV3 and A2780, and the glucose consumption, lactate production and PKM2 protein level were detected. Dual-luciferase reporter assay and RIP were utilized to verify the direct binding of H19 to miR-324-5p and miR-324-5p to PKM2. Cell proliferation was examined by CCK8 and colony formation assay. Nude mice subcutaneous xenograft tumor models were established to evaluate the impact of miR-324-5p on tumor growth in vivo. Results: 20(S)-Rg3 downregulated 67 lncRNAs, and H19 was one of the most decreased lncRNAs. Suppression of H19 by siRNA transfection reduced glucose consumption, lactate production and PKM2 expression in ovarian cancer cells, while H19 overexpression in 20(S)-Rg3-treated ovarian cancer cells enhanced glucose consumption, lactate production and PKM2 expression. Dual-luciferase reporter assay and RIP results showed that H19 directly bound to miR-324-5p. Dual-luciferase reporter assay showed that miR-324-5p directly targeted PKM2, and miR-324-5p negatively regulated glucose consumption and lactate production in ovarian cancer cells. miR-324-5p overexpression inhibited cell proliferation in vitro and in vivo. Conclusion: Our study revealed that 20(S)-Rg3 blocked the competitive inhibition of H19 on miR-324-5p, which enhanced the suppression of miR-324-5p on PKM2 and therefore inhibited the Warburg effect and repressed tumorigenesis. In a word, 20(S)-Rg3 inhibited the Warburg effect in ovarian cancer cells via H19/miR-324-5p/PKM2 pathway.

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“…UCA1 promotes BC progression through the PI3K/Akt/ CREB pathway [9], enhances BC migration and invasion by the miR-145/FSCN1/Zeb1/Zeb2 network [10], and is involved in regulation of the Warburg effect through the mTOR/STAT3/ miR-143 /HK2 signaling pathway [11]; these findings strongly demonstrate that UCA1 acts as an oncogene in BC development. The results showed that UCA1 participates in regulation of the Warburg effect in BC.…”

Section: Introductionmentioning

confidence: 99%

LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway

Sun

et al. 2017

Cell Physiol Biochem

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102

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Background/Aims: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. Methods: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5’,6,6’-tetrachloro-1,1’,3,3’- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. Results: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. Conclusion: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.

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Long non‐coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR–STAT3/microRNA143 pathway

Cited by 222 publications

References 29 publications

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells

LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway

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