Long Non-coding Wilms Tumor 1 Antisense RNA in the Development and Progression of Malignant Tumors

Zhang, Ye; Fan, Liancheng; Zhang, Yi; Jiang, Jun; Qi, Xiaowei

doi:10.3389/fonc.2020.00035

Cited by 12 publications

(13 citation statements)

References 33 publications

(45 reference statements)

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“…Thus, these common lncRNAs may have high potential for future HNC-specific studies. On the other hand, some lncRNAs from our panel are relatively novel lncRNAs, such as WT1-AS, where only a handful of studies have proposed its carcinogenic function in lung, cervical, and breast cancer ( 36 – 38 ). Knowledge regarding HOXA11-AS is also sparse, although recent studies have elaborated on its role in liver ( 39 ), lung ( 40 ), head-neck ( 34 ), and other cancers ( 41 ).…”

Section: Discussionmentioning

confidence: 98%

Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer

Tang

You²,

Chang³

et al. 2021

Front. Oncol.

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Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.

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Section: Discussionmentioning

confidence: 98%

Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer

Tang

You²,

Chang³

et al. 2021

Front. Oncol.

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“…Except for binding to microRNAs or RBPs, lncRNAs could regulate protein translation and modification directly. 37 For instance, the antisense RNA of wilms Tumor 1 Antisense RNA (WT1-AS) could maintain the stability and regulate the translation of WT1 mRNA. 37 Thus, we thought that TBX5-AS1 might regulate some certain downstream gene.…”

Section: Dovepressmentioning

confidence: 99%

“…37 For instance, the antisense RNA of wilms Tumor 1 Antisense RNA (WT1-AS) could maintain the stability and regulate the translation of WT1 mRNA. 37 Thus, we thought that TBX5-AS1 might regulate some certain downstream gene. In previous studies, a number of antisense RNAs has been revealed to affect the cell phenotypes by modulating the PI3K/AKT pathway.…”

Section: Dovepressmentioning

confidence: 99%

<p>LncRNA <em>TBX5-AS1</em> Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer</p>

Qing-hai¹,

Jiang²,

Li³

2020

OTT

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Long non-coding RNAs (lncRNAs) have been reported to play important roles in tumor biology. In this study, we aimed to investigate the effects of T-box transcription factor 5 antisense RNA 1 (TBX5-AS1) on aggressive phenotypes of non-small cell lung cancer (NSCLC) cells and explore its regulatory pathway. Methods: The expression of TBX5-AS1 in tissues, plasma, and cells was determined by qRT-PCR. Cell viability, proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, wound-healing, Transwell, and flow cytometry assay, respectively. Western blot analysis was performed to measure the expression of apoptosis-related proteins. Besides, transfected cells were exposed to PI3K activator (740Y-P) to verify the regulatory pathway. Results: TBX5-AS1 expression was down-regulated in NSCLC tissues, plasma, and cells, and associated with lymph node metastasis and histological grade. Overexpression of TBX5-AS1 inhibited cell viability, colony formation, migration, and invasion, while it promoted apoptosis. Conversely, knockdown of TBX5-AS1 showed the completely opposite results. Additionally, western blot showed that the phosphorylation of PI3K and AKT was stimulated by TBX5-AS1 knockdown and suppressed by TBX5-AS1 overexpression. The addition of 740Y-P in transfected cells reversed the TBX5-AS1induced inhibition of PI3K and AKT phosphorylation and effects on aggressive phenotypes of NSCLC cells. Conclusion: The study confirmed the down-regulation of TBX5-AS1 in patients with NSCLC and its association with the progression. We innovatively proposed a possible model of TBX5-AS1-mediated gene regulation in NSCLC progression that TBX5-AS1 inhibited the aggressive phenotypes of NSCLC cells through inactivating the PI3K/AKT pathway. This finding provided a novel insight into NSCLC pathogenesis.

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“…The human WT1 gene is associated with an antisense non-coding RNA (ncRNA), WT1-AS, which we have previously shown to be spatially and temporally regulated coordinately with and in vitro. It is capable of upregulating WT1 protein level [1]. WT1 long non-coding RNA has been related to malignant progression in a wide variety of neoplasias [2].…”

Section: Introductionmentioning

confidence: 99%

The Human Long Noncoding RNA Wilms Tumour 1 Antisense Locus, from an Evolutionary Perspective to Functional Insights

Meza

Lozada-Grajales

Rasool

et al. 2022

Preprint

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The Wilms’ tumor suppressor gene 1 (WT1) encodes a structurally diverse and multifunctional protein with tightly controlled expression throughout the development of several organ systems, particularly essential for genitourinary development, sex determination, as well as nephrogenesis. How WT1 locus contributes to the shift from normal function nor developmental disease is not well understood. Bidirectional sense and antisense transcription are abundant across vertebrates suggesting that antisense transcripts may be relevant, but their biological function is largely unknown. However, the analysis of a novel knock-out mouse demonstrated that an ultra-conserved WT1 transcript RNA (UCWT2) stabilizes Awt1 RNA expression and displays phenotypic changes, resulting in changes at embryonic survival, as well as liquid homeostasis. We demonstrate that WT1 antisense transcript evolutionary parallels vertebrate morphological urinary systems and may act as regulator in WT1 locus, implying a physiological effect, from in silico to in vitro tools.

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Long Non-coding Wilms Tumor 1 Antisense RNA in the Development and Progression of Malignant Tumors

Cited by 12 publications

References 33 publications

Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer

Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer

<p>LncRNA <em>TBX5-AS1</em> Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer</p>

The Human Long Noncoding RNA Wilms Tumour 1 Antisense Locus, from an Evolutionary Perspective to Functional Insights

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