Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma

Li, Yongsheng; Wang, Zishan; Wang, Yuan; Zhao, Zheng; Zhang, Jinwen; Lu, Jianping; Xu, Juan; Li, Xia

doi:10.18632/oncotarget.7801

Cited by 38 publications

(35 citation statements)

References 61 publications

(66 reference statements)

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“…Non-coding RNAs (including both miRNAs and lncRNAs) have been recently implicated as important regulators of various tumorigenic processes including GBM [ 23 , 25 , 30 ]. Although most studies have explored the roles of miRNAs [ 40 ], recent reports implicated specific lncRNAs as critical factors in determining GBM growth, infiltration and response to therapies [ 23 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…The expression of lncRNAs has been recently characterized in GBM [ 22 , 23 ] and lncRNA signatures and profiles in various GBM subtypes [ 24 ] and in association with patient prognosis [ 25 , 26 ] have been identified. Moreover, the roles of specific lncRNAs such as H19 [ 27 ] and MALAT1 [ 28 ] have been described in various functions of glioma cells [ 29 , 30 ], whereas the function of lncRNAs in the functions of GSCs is just beginning to be understood.…”

Section: Introductionmentioning

confidence: 99%

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The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells

Brodie

Lee²,

Jiang³

et al. 2017

Oncotarget

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Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell proliferation and arrested the cells in the G1\S phase of the cell cycle in various cancer cell lines. In addition, silencing of TALNEC2 decreased the self-renewal and mesenchymal transformation of GSCs, increased sensitivity of these cells to radiation and prolonged survival of mice bearing GSC-derived xenografts. Using miRNA array analysis, we identified specific miRNAs that were altered in the silenced cells that were associated with cell-cycle progression, proliferation and mesenchymal transformation. Two of the downregulated miRNAs, miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM and in tumors from patients of short-term survival. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells

Brodie

Lee²,

Jiang³

et al. 2017

Oncotarget

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show abstract

“…However, some other regulatory issues (such as transcription factors or miRNAs) still need to be addressed for investigate the detail mechanism. In addition, the mechanisms of action of lncRNAs are diverse and include RNA-RNA, RNA-DNA, and RNAprotein interactions [45]. Evidence has shown that MIR22HG is a target of miR-141-3p in endometrial carcinoma [46].…”

Section: Discussionmentioning

confidence: 99%

MIR22HG acts as a tumor suppressor via TGFβ/SMAD signaling and facilitates immunotherapy in colorectal cancer

Shao

Song

et al. 2020

Mol Cancer

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Background: Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC). Methods: Differentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo. Results:We systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFβ pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy. Conclusion: MIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFβ pathway and facilitates immunotherapy in cancer.

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“…In this study, we established a computational method for identification the modulators whose expression is associated with changing the targets splicing outcomes of RBPs in KIRC. Previously, several computational methods have been developed to identify modulators associated with transcription factors (TFs) regulation activity on expression level (Wang et al, 2009;Babur et al, 2010;Li et al, 2016Li et al, , 2017, these studies discussed the transcriptional activities of TFs can be influenced by the expression level of modulators. Our method is unique in its ability to discover how alternative splicing outcomes is changing when modulator expression is different, even though they were regulated by the same RBP.…”

Section: Discussionmentioning

confidence: 99%

Modulator-Dependent RBPs Changes Alternative Splicing Outcomes in Kidney Cancer

et al. 2020

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Alternative splicing alterations can contribute to human disease. The ability of an RNAbinding protein to regulate alternative splicing outcomes can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we use a computational framework to investigate the roles of certain genes, termed modulators, on changing RBPs' effect on splicing regulation. A total of 1,040,254 modulator-mediated RBP-splicing interactions were identified, including 137 RBPs, 4,309 splicing events and 2,905 modulator candidates from TCGA-KIRC RNA sequencing data. Modulators function categories were defined according to the correlation changes between RBPs expression and their targets splicing outcomes. QKI, as one of the RBPs influencing the most splicing events, attracted our attention in this study: 2,014 changing triplets were identified, including 1,101 modulators and 187 splicing events. Pathway enrichment analysis showed that QKI splicing targets were enriched in tight junction pathway, endocytosis and MAPK signaling pathways, all of which are highly associated with cancer development and progression. This is the first instance of a comprehensive study on how alternative splicing outcomes changes are associated with different expression level of certain proteins, even though they were regulated by the same RBP. Our work may provide a novel view on understanding alternative splicing mechanisms in kidney cancer.

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Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma

Cited by 38 publications

References 61 publications

The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells

The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells

MIR22HG acts as a tumor suppressor via TGFβ/SMAD signaling and facilitates immunotherapy in colorectal cancer

Modulator-Dependent RBPs Changes Alternative Splicing Outcomes in Kidney Cancer

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