Nkx2-2as Suppression Contributes to the Pathogenesis of Sonic Hedgehog Medulloblastoma

Zhang, Yimeng; Wang, Ting; Wang, Shan; Xiong, Yanlu; Zhang, Rui; Zhang, Xiang; Zhao, Jing; Yang, An‐Gang; Wang, Lei; Jia, Lintao

doi:10.1158/0008-5472.can-17-1631

Cited by 36 publications

(30 citation statements)

References 44 publications

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“…FOXD1 is associated with cell programming, especially in renal and kidney development [7][8][9][10]. Abnormal FOXD1 expression is involved in the progression of tumors [11] including breast cancer [12], colorectal cancer, melanoma, glioma [13], osteosarcoma, renal cell carcinoma, ovarian carcinoma, medulloblastoma [14], and lung cancer [15]. Recently, clinical mRNA microarray data identified FOXD1 as a factor associated with poor prognosis and that is required for lung cancer cell proliferation [15].…”

Section: Introductionmentioning

confidence: 99%

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Chang

Hsiao

et al. 2019

Cancers

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Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with the Gal-3 promoter to upregulate Gal-3 in FOXD1-overexpressing CL1-0 lung cancer cells. Ectopic expression of FOXD1 increased the expression of Gal-3 and the growth and motility of lung cancer cells, whereas depletion of Gal-3 attenuated FOXD1-mediated tumorigenesis. ERK1/2 interacted with FOXD1 in the cytosol and translocated FOXD1 into the nucleus to activate Gal-3. Gal-3 in turn upregulated FOXD1 via the transcription factor proto-oncogene 1 (ETS-1) to transactivate FOXD1. The increase in ETS-1/FOXD1 expression by Gal-3 was through Gal-3-mediated integrin-β1 (ITGβ1) signaling. The overexpression of both FOXD1 and Gal-3 form a positive regulatory loop to promote lung cancer aggressiveness. Moreover, both FOXD1 and Gal-3 were positively correlated in human lung cancer tissues. Our findings demonstrated that FOXD1 and Gal-3 form a positive feedback loop in lung cancer, and interference of this loop may serve as an effective therapeutic target for the treatment of lung cancers, particularly those related to dysregulation of Gal-3.

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Section: Introductionmentioning

confidence: 99%

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Chang

Hsiao

et al. 2019

Cancers

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“…NKX2-2AS was shown in vitro to modulate SHH-potentiated MB development by acting as a miRNA sponge for miR-103 and miR-107, thereby depressing their tumor suppressive targets BTG2 and LATS1 and inhibiting proliferation and migration [42]. CDKN2B-AS1 (ANRIL) has been shown to promote proliferation in vitro studies by sponging miR-323 and activating BRI3 dependent p38-MAPK, AKT and WNT signaling [43], and in current analysis, it was found to be upregulated in group 4 patients compared to other MBs.…”

Section: Discussionmentioning

confidence: 99%

In silico analysis of long non-coding RNAs in medulloblastoma and its subgroups

Joshi

Perera

2019

Preprint

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AbstractMedulloblastoma is the most common malignant pediatric brain tumor with high fatality rate. Recent large-scale studies utilizing genome-wide technologies have sub-grouped medulloblastomas into four major subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. However, there has yet to be a global analysis of long non-coding RNAs, a crucial part of the regulatory transcriptome, in medulloblastoma. Here, we performed bioinformatic analysis of RNA-seq data from 175 medulloblastoma patients. Differential lncRNA expression sub-grouped medulloblastomas into the four main molecular subgroups. Some of these lncRNAs were subgroup-specific, with a random forest-based machine-learning algorithm identifying an 11-lncRNA diagnostic signature. We also validated the diagnostic signature in patient derived xenograft (PDX) models. We further identified a 17-lncRNA prognostic model using LASSO based penalized Cox’ PH model (Score HR= 13.6301, 95% CI= 8.857-20.98, logrank p-value=< 2e-16). Our analysis represents the first global lncRNA analysis in medulloblastoma. Our results identify putative candidate lncRNAs that could be evaluated for their functional role in medulloblastoma genesis and progression or as diagnostic and prognostic biomarkers.

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“…In MB, it was also observed that lncRNA Nkx2-2as depress tumor suppressing targets BTG2 and LATS1 in the SHH subgroup of MB by competing with miR-103 and miR-107 and impeding cell proliferation and migration [ 181 ]. Knockdown of oncogenic lnc-IRX3-80 (CRNDE) inhibited tumor growth, significantly reduced cell proliferation, and increased the level of apoptosis in MB cell lines [ 182 ].…”

Section: Diagnostic and Therapeutic Potential Of Ncrnasmentioning

confidence: 99%

Non-Coding RNAs in Brain Tumors, the Contribution of lncRNAs, circRNAs, and snoRNAs to Cancer Development—Their Diagnostic and Therapeutic Potential

Latowska

Grabowska

Zarębska

et al. 2020

IJMS

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Brain tumors are one of the most frightening ailments that afflict human beings worldwide. They are among the most lethal of all adult and pediatric solid tumors. The unique cell-intrinsic and microenvironmental properties of neural tissues are some of the most critical obstacles that researchers face in the diagnosis and treatment of brain tumors. Intensifying the search for potential new molecular markers in order to develop new effective treatments for patients might resolve this issue. Recently, the world of non-coding RNAs (ncRNAs) has become a field of intensive research since the discovery of their essential impact on carcinogenesis. Some of the most promising diagnostic and therapeutic regulatory RNAs are long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs). Many recent reports indicate the important role of these molecules in brain tumor development, as well as their implications in metastasis. In the following review, we summarize the current state of knowledge about regulatory RNAs, namely lncRNA, circRNAs, and snoRNAs, and their impact on the development of brain tumors in children and adults with particular emphasis on malignant primary brain tumors—gliomas and medulloblastomas (MB). We also provide an overview of how these different ncRNAs may act as biomarkers in these tumors and we present their potential clinical implications.

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Nkx2-2as Suppression Contributes to the Pathogenesis of Sonic Hedgehog Medulloblastoma

Cited by 36 publications

References 44 publications

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

In silico analysis of long non-coding RNAs in medulloblastoma and its subgroups

Non-Coding RNAs in Brain Tumors, the Contribution of lncRNAs, circRNAs, and snoRNAs to Cancer Development—Their Diagnostic and Therapeutic Potential

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