Dataset Information

SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically.

ABSTRACT: Long noncoding RNA CUDR plays an important role during tumorigenesis. Herein, we demonstrate that SET1A cooperates with CUDR to accelerate hepatocarcinogenesis and promote malignant transformation of hepatocyte-like stem cells. Mechanistically, CUDR enhances the phosphorylation of RB1, C-myc expression, and the interplay between the SET1A and pRB1. Notably, CUDR acts as a sponge cushion that shows a link between SET1A and pRB1, producing a activated pRB1-SET1A complex. On the other hand, the pRB1-SET1A complex may carry methyls(me) to occupy the position of H3K4, resulting in specific tri-methylation of forth lysine of histone H3 (H3K4me3). Thereby, the H3K4me3 loads on the TRF2 promoter region which causes the TRF2 overexpression. Ultimately, the excessive TRF2 binds to telomere repeat DNA, prolonging the telomere length. These findings provide the first demonstration that SET1A cooperates with CUDR to play a positive potential role during hepatocarcinogenesis and hepatocyte-like stem cells' malignant transformation epigenetically.

SUBMITTER: Li T

PROVIDER: S-EPMC4817816 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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RETRACTED: SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically

Li Tianming T Zheng Qidi Q An Jiahui J Wu Mengying M Li Haiyan H Gui Xin X Pu Hu H Lu Dongdong D

Molecular therapy : the journal of the American Society of Gene Therapy 20151119 2

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the editor-in-chief. Similarities were found between images in this article and an article in Oncotarget (Pu et al., 2015, Oncotarget 6, 40775-40798, https://doi.org/10.18632/oncotarget.5905) previously published by the same authors. Similarities were also found between images within this article. Image analysis pe ...[more]

PMID: 26581161

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Project description:Rationale: Colitis-associated colorectal cancer (CAC) usually exhibits an accelerated disease progression, an increased resistance to therapeutic drugs and a higher mortality rate than sporadic colorectal cancer (CRC). PIAS3 is a member of the protein inhibitor of activated STAT (PIAS) family; however, little is known about the expression and biological functions of PIAS3 in CAC. The aim of our study was to investigate the biological mechanisms of PIAS3 in CAC. Methods: PIAS3 expression was examined in colon tissues of CAC/CRC patients and azoxymethane-dextran sulfate sodium (AOM-DSS)-induced mice. The role of PIAS3 was studied using a series of in vitro, in vivo and clinical approaches. Results: Downregulated PIAS3 expression, upregulated miR-18a expression and highly activated NF-κB and STAT3 were observed in colon tissues of CAC/CRC patients and AOM-DSS-induced mice. In vitro experiments revealed that PIAS3 significantly inhibited the activation of NF-κB and STAT3 and demonstrated that activated NF-κB and STAT3 transcriptionally regulated miR-18a level, and up-regulation of miR-18a expression led to defective PIAS3 expression. Moreover, PIAS3-mediated autoregulatory feedback loops (PIAS3/NF-κB/miR-18a and PIAS3/STAT3/miR-18a) were verified in vitro and were found to regulate cell proliferation. Additionally, modulation of the feedback loops via overexpression of PIAS3 or knockdown of miR-18a significantly inhibited cell proliferation in a mouse CRC xenograft model. Furthermore, upregulation of PIAS3 by intracolonic administration of PIAS3 lentivirus or anti-miR-18a lentivirus in AOM-DSS-induced mice led to dramatically reduced tumor sizes/numbers, whereas knockdown of PIAS3 in CAC mice significantly promoted tumor growth. Conclusion: Our data clearly show that PIAS3-mediated feedback loops control cell proliferation and function as robust driving forces for CAC progression. Targeting these highly activated feedback loops might offer promising therapeutic strategies for CAC.

Dataset Information

SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically.

Publications

RETRACTED: SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically

Similar Datasets

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