Micro<scp>RNA</scp>‐198‐5p inhibits the migration and invasion of non‐small lung cancer cells by targeting fucosyltransferase 8

Wang, Siyao; Zhang, Xin; Yang, Chunrong; Xu, Shun

doi:10.1111/1440-1681.13154

Cited by 25 publications

(17 citation statements)

References 34 publications

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“…The fucosyltransferase (FUT) family are the key enzymes in cell-surface antigen synthesis during various biological processes such as tumor proliferation, metastasis and drug resistance (18,19). At present, a total of 13 members consisted FUT1 to FUT11, protein O-fucosyltransferase 1 (POFUT1) and POFUT2 were identified.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

Cao

Zeng

Pan³

et al. 2021

Front. Oncol.

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BackgroundHypoxia is associated with the development of pancreatic cancer (PC). However, genes associated with hypoxia response and their regulatory mechanism in PC cells were unclear. The current study aims to investigate the role of the hypoxia associated gene fucosyltransferase 11 (FUT11) in the progression of PC.MethodsIn the preliminary study, bioinformatics analysis predicted FUT11 as a key hypoxia associated gene in PC. The expression of FUT11 in PC was evaluated using quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation and migration under normoxia and hypoxia were evaluated using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine (EDU) assay, colony formation assay and transwell assay. The effects of FUT11 in vivo was examined in mouse tumor models of liver metastasis and subcutaneous xenograft. Furthermore, Western blot, luciferase assay and immunoprecipitation were performed to explore the regulatory relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC.ResultsFUT11 was markedly increased of PC cells with hypoxia, upregulated in the PC clinical tissues, and predicted a poor outcome of PC patients. Inhibition of FUT11 reduced PC cell growth and migratory ability of PC cells under normoxia and hypoxia conditions in vitro, and growth and tumor cell metastasis in vivo. FUT11 bound to PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 interacted with PDK1 and decreased the ubiquitination of PDK1, lead to the activation of AKT/mTOR signaling pathway. FUT11 knockdown significantly increased the degradation of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressive impacts of FUT11 knockdown on PC cell growth and migration. In addition, HIF1α bound to the promoter of FUT11 and increased its expression, as well as co-expressed with FUT11 in PC tissues. Furthermore, overexpression of FUT11 partially rescued the suppressive effects of HIF1α knockdown on PC cell growth and migration in hypoxia condition.ConclusionOur data implicate that hypoxia-induced FUT11 contributes to proliferation and metastasis of PC by maintaining the stability of PDK1, thus mediating activation of AKT/mTOR signaling pathway, and suggest that FUT11 could be a novel and effective target for the treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

Cao

Zeng

Pan³

et al. 2021

Front. Oncol.

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show abstract

“…The fucosyltransferase (FUT) family is the key enzymes in cell-surface antigen synthesis during various biological processes such as tumor resistance, proliferation and metastasis [20,21]. Until now, total 13 members contained FUT1 to FUT11, protein O-fucosyltransferase 1 (POFUT1) and POFUT2 were identi ed.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-related gene FUT11 promoted pancreatic cancer progression via maintaining the stabilization of PDK1

Cao¹,

Zeng

Pan³

et al. 2021

Preprint

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Background Hypoxia participated in the occurrence and development of pancreatic cancer (PC). However, genes associated with hypoxia respond and their regulated mechanism in PC cells were unclear. The current research was aimed to illuminate the role and hypoxia regulated mechanism of fucosyltransferase 11 (FUT11) in the progression of PC. Methods After predicting FUT11 as a key hypoxia associated gene in PC using bioinformatics analysis. The expression of FUT11 in PC using quantitative real-time fluorescent PCR, western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation and migration under normoxia and hypoxia were detected using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine assay, colony formation assay and transwell assay. Spleen capsule injected liver metastasis and subcutaneously injected model were performed to confirm the effects of FUT11 in vivo. Furthermore, western blot, luciferase assay and immunoprecipitation were performed to explore the regulated relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC. Results FUT11 was markedly increased of PC cells in hypoxia, up-regulated in the PC clinical tissues, and predicted a poor outcome. Inhibition of FUT11 reduced PC cell growth and mobility of PC cells under normoxia and hypoxia conditions in vitro, and growth and mobility in vivo. FUT11 bind with PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 knockdown significantly increased the degradation rate of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressiv impacts of FUT11 knockdown on PC cell growth and mobility. In addition, HIF1α bound to the enhancer of FUT11 and increased its expression, as well as co-expressing with FUT11 in PC tissues. Furthermore, overexpress of FUT11 partially rescued the suppressiv effects of HIF1α knockdown on PC cell growth and mobility in hypoxia conditions. Conclusion Our data further implicate that hypoxia-induced FUT11 in PC contributes to proliferation and metastasis by maintaining the stability of PDK1, and suggest FUT11 maybe a novel and effective target for treatment of pancreatic cancer.

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“…Lung cancer can be divided into two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer. NSCLC can be further divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, accounting for about 80% of all lung cancer cases 2,3 . However, the main means of cancer treatment is still surgery combined with radiotherapy and chemotherapy 4 .…”

Section: Introductionmentioning

confidence: 99%

The mechanism of m6A methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by β-elemene

et al. 2020

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N6-methyladenosine (m6A) modification can alter gene expression by regulating RNA splicing, stability, translocation, and translation. Emerging evidence shows that m6A modification plays an important role in cancer development and progression, including cell proliferation, migration and invasion, cell apoptosis, autophagy, and drug resistance. Until now, the role of m6A modification mediated autophagy in cancer drug resistance is still unclear. In this study, we found that m6A methyltransferase METTL3-mediated autophagy played an important role in reversing gefitinib resistance by β-elemene in non-small cell lung cancer (NSCLC) cells. Mechanistically, in vitro and in vivo studies indicated that β-elemene could reverse gefitinib resistance in NSCLC cells by inhibiting cell autophagy process in a manner of chloroquine. β-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. Moreover, both β-elemene and gefitinib decreased the level of m6A methylation of gefitinib resistance cells. METTL3 was higher expressed in lung adenocarcinoma tissues than that of paired normal tissues, and was involved in the gefitinib resistance of NSCLC cells. Furthermore, METTL3 positively regulated autophagy by increasing the critical genes of autophagy pathway such as ATG5 and ATG7. In conclusion, our study unveiled the mechanism of METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by β-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

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MicroRNA‐198‐5p inhibits the migration and invasion of non‐small lung cancer cells by targeting fucosyltransferase 8

Cited by 25 publications

References 34 publications

Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

Hypoxia-related gene FUT11 promoted pancreatic cancer progression via maintaining the stabilization of PDK1

The mechanism of m6A methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by β-elemene

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