LncRNA-NEF antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/β-catenin signaling

Oncogene
Wei-Cheng LiangJin-Fang Zhang

Abstract

Emerging evidence indicates that the long noncoding RNAs extensively participate in cancer progression. Nevertheless, the molecular pathogenesis of how these lncRNAs regulate tumorigenesis has not been fully elucidated especially in hepatocellular carcinoma (HCC). Here, we sought to define the role of a novel lncRNA named lncRNA-NEF in modulating epithelial to mesenchymal transition (EMT) in HCC. It was found that the lncRNA-NEF was transcriptionally activated by EMT suppressor FOXA2 and frequently downregulated in HCC cell lines as well as clinical specimens. Although enhanced expression of lncRNA-NEF did not affect tumor cell growth, ectopic expression of lncRNA-NEF significantly suppressed EMT program and cell migration. Animal studies validated that lncRNA-NEF alleviated in vivo tumor metastasis and protected mice from tumor-induced mortality. Interestingly, we verified that lncRNA-NEF acted as a novel activator of its neighbor gene FOXA2, which formed a positive feedback loop. Subsequent studies revealed that lncRNA-NEF physically interacted with β-catenin to increase the binding of GSK3β with β-catenin and therefore promoted the inhibitory phosphorylation of β-catenin, leading to the suppression on Wnt/β-catenin signaling...Continue Reading

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Citations

Jun 22, 2019·The Journal of International Medical Research·Xiaoyong MaWenkui Zheng
Sep 7, 2019·Pathology Oncology Research : POR·Prit Benny MalgulwarMehar Chand Sharma
May 26, 2020·Journal of Cellular and Molecular Medicine·Hanfang CaiHong Chen
Jan 6, 2019·Archives of Pharmacal Research·Mi Jeong HeoSang Geon Kim
Dec 26, 2018·Journal of Cellular Biochemistry·Zhihui LiuXiaojie Song
Mar 7, 2019·Acta Biochimica Et Biophysica Sinica·Xiang SongZhiyong Yu
Jul 2, 2019·Experimental and Therapeutic Medicine·Qiao HuangYuenan Yang
Apr 17, 2020·Molecular Cancer·Zhao HuangCanhua Huang
May 18, 2019·Journal of Experimental & Clinical Cancer Research : CR·Haoming MaiDeke Jiang
Sep 10, 2019·Journal of Clinical Laboratory Analysis·Yang ChenDi Tang
Nov 2, 2020·Cancer Letters·Chen XieJin-E Yang
Dec 8, 2020·Frontiers in Genetics·Suryaji PatilAirong Qian
Mar 9, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Wenxiao JiangXueqiong Zhu
May 7, 2021·Nature Reviews. Cancer·S John LiuChristopher A Maher
Jun 12, 2021·Frontiers in Oncology·Xiaoyong GeXinwei Han

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Methods Mentioned

BETA
heterologous transcription assay
immunoprecipitation
ChIP
ChIP-seq
xenograft
RNA-seq
immunoprecipitation assay
co-IP
biopsies

Software Mentioned

DAVID
Image J

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