Genome-wide identification of key regulatory lncRNAs in esophageal cancer metastasis

Xu, Wen; Zheng, Can‐Can; Zuo, Qian; Li, Junqi; Pan, Hong; Qin, Yanru; Guan, Xin‐Yuan; He, Qing‐Yu; Liao, Hua‐Xin; Li, Bin

doi:10.1038/s41392-021-00476-9

Cited by 16 publications

(12 citation statements)

References 5 publications

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“…Immunohistochemistry was performed as described previously 15 . The expression of PFKL was analyzed in the tissue microarray including 206 ESCC tissues and 135 corresponding normal tissues (Shanghai Outdo Biotech, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

Zheng

Liang

et al. 2022

Acta Pharmaceutica Sinica B

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Section: Methodsmentioning

confidence: 99%

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

Zheng

Liang

et al. 2022

Acta Pharmaceutica Sinica B

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“…In the past few decades, considerable efforts have been made to investigate the molecular mechanisms underlying ESCC pathogenesis [ 9 , 10 ]. Both genetic, including mutations in tumor suppressor genes such as TP53 and NFE2L2 [ 11 , 12 ], and epigenetic alterations, including DNA methylation and non-coding RNAs [ 13 – 15 ], have been uncovered to play pivotal roles in the tumorigenesis and development of ESCC. Multi-faced imbalance of gene expression, such as proto-oncogene amplification, mutations, deletions, and epigenetic modifications, could work together to maintain the malignant biological characteristics of ESCC [ 12 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

RNA m6A demethylase FTO-mediated epigenetic up-regulation of LINC00022 promotes tumorigenesis in esophageal squamous cell carcinoma

Cui

Zhang

et al. 2021

J Exp Clin Cancer Res

100

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Background Long non-coding RNA (LncRNA) controls cell proliferation and plays a significant role in the initiation and progression of esophageal squamous cell carcinoma (ESCC). N6-methyladenosine (m6A) modification now is recognized as a master driver of RNA function to maintain homeostasis in cancer cells. However, how m6A regulates LncRNA function and its role in tumorigenesis of ESCC remain unclear. Methods Multiple ESCC datasets were used to analyze gene expression in tumor tissues and normal tissues. Kaplan-Meier method and the ROC curve were conducted to evaluate the prognostic value and diagnostic value of LINC00022 in ESCC, respectively. Both gain-of-function and loss-of-function experiments were employed to investigate the effects of LINC00022 on ESCC growth in vitro and in vivo. Bioinformatics analysis, colorimetric m6A assay, RIP, MeRIP and co-IP was performed to explore the epigenetic mechanism of LINC00022 up-regulation in ESCC. Results Here we report that m6A demethylation of LncRNA LINC00022 by fat mass and obesity-associated protein (FTO) promotes tumor growth of ESCC in vivo. Clinically, we revealed that LINC00022 was up-regulated in primary ESCC samples and was predictive of poor clinical outcome for ESCC patients. Mechanistically, LINC00022 directly binds to p21 protein and promotes its ubiquitination-mediated degradation, thereby facilitating cell-cycle progression and proliferation. Further, the elevated FTO in ESCC decreased m6A methylation of LINC00022 transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2. Over-expression of FTO was shown to drive LINC00022-dependent cell proliferation and tumor growth of ESCC. Conclusions Thus, this study demonstrated m6A-mediated epigenetic modification of LncRNA contributes to the tumorigenesis in ESCC and LINC00022, specific target of m6A, serves as a potential biomarker for this malignancy.

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“…Furthermore, lncRNA could sequester miRNAs to modulate the gene expression [ 36 – 39 ]. Specifically, Tong et al .…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

Yang

Liu

et al. 2021

J Transl Med

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Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

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Genome-wide identification of key regulatory lncRNAs in esophageal cancer metastasis

Cited by 16 publications

References 5 publications

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

RNA m6A demethylase FTO-mediated epigenetic up-regulation of LINC00022 promotes tumorigenesis in esophageal squamous cell carcinoma

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

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