Dataset Information

A novel long noncoding RNA PILRLS promote proliferation through TCL1A by activing MDM2 in Retroperitoneal liposarcoma.

ABSTRACT: It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in retroperitoneal liposarcoma have never been reported. In our study, we found a novel lncRNA PILRLS (Proliferation Interacting LncRNA in Retroperitoneal Liposarcoma), which as an oncogene significantly overexpressed in retroperitoneal liposarcoma. Functions of PILRLS on tumor progression both in vitro and in vivo have verified in this study which PILRLS knockdown significantly inhibited cell proliferation and colony formation. RNA pull-down assay found PILRLS can specific binding with TCL1A which also regulate the expression level of TCL1A. Our work for the first time demonstrated PILRLS can activating the MDM2 by binding with TCL1A which suppress the P53 pathway to promote the unlimited growth of retroperitoneal Liposarcoma cells. It suggests that PILRLS may be an important targets for retroperitoneal liposarcoma therapy.

SUBMITTER: Shao Y

PROVIDER: S-EPMC5355154 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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A novel long noncoding RNA PILRLS promote proliferation through TCL1A by activing MDM2 in Retroperitoneal liposarcoma.

Shao Yebo Y Zhang Yong Y Hou Yingyong Y Tong Hanxing H Zhuang Rongyuan R Ji Zhengbiao Z Wang Binliang B Zhou Yuhong Y Lu Weiqi W

Oncotarget 20170201 8

It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in retroperitoneal liposarcoma have never been reported. In our study, we found a novel lncRNA PILRLS (Proliferation Interacting LncRNA in Retroperitoneal Liposarcoma), which as an oncogene significantly overexpressed in retroperitoneal liposarcoma. Functions of PILRLS on tumor progression both in vitro and in vivo ...[more]

PMID: 28129655

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Project description:Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Long noncoding RNA (lncRNA) plays a critical role in the development and progression of multiple human cancers. However, the function of lncRNA in HTLV-1-induced oncogenesis has not been elucidated. In the present study, we show that the expression level of the lncRNA ANRIL was elevated in HTLV-1-infected cell lines and clinical ATL samples. E2F1 induced ANRIL transcription by enhancing its promoter activity. Knockdown of ANRIL in ATL cells repressed cellular proliferation and increased apoptosis in vitro and in vivo As a mechanism for these actions, we found that ANRIL targeted EZH2 and activated the NF-?B pathway in ATL cells. This activation was independent of the histone methyltransferase (HMT) activity of EZH2 but required the formation of an ANRIL/EZH2/p65 ternary complex. A chromatin immunoprecipitation assay revealed that ANRIL/EZH2 enhanced p65 DNA binding capability. In addition, we observed that the ANRIL/EZH2 complex repressed p21/CDKN1A transcription through H3K27 trimethylation of the p21/CDKN1A promoter. Taken together, our results implicate that the lncRNA ANRIL, by cooperating with EZH2, supports the proliferation of HTLV-1-infected cells, which is thought to be critical for oncogenesis.IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes adult T-cell leukemia (ATL), which is a unique malignancy of CD4+ T cells. A role for long noncoding RNA (lncRNA) in HTLV-1-mediated cellular transformation has not been described. In this study, we demonstrated that the lncRNA ANRIL was important for maintaining the proliferation of ATL cells in vitro and in vivo ANRIL was shown to activate NF-?B signaling through forming a ternary complex with EZH2 and p65. Furthermore, epigenetic inactivation of p21/CDKN1A was involved in the oncogenic function of ANRIL. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA ANRIL in ATL and provides an important clue to prevent or treat HTLV-1-associated human diseases.

Dataset Information

A novel long noncoding RNA PILRLS promote proliferation through TCL1A by activing MDM2 in Retroperitoneal liposarcoma.

Publications

A novel long noncoding RNA PILRLS promote proliferation through TCL1A by activing MDM2 in Retroperitoneal liposarcoma.

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