Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers

Liu, Ji‐Long; Zhang, Wen‐Qian; Zhao, Miao; Huang, Mingyu

doi:10.1002/jcp.27400

Cited by 15 publications

(12 citation statements)

References 26 publications

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“…XIST appears to be both tumor-promoting and tumorsuppressive, depending on cancer type and context [118]. Surprisingly, two meta-analyses of XIST in cancer identified no association between XIST and sex/gender, but did find that high levels were associated with poor overall survival [119,120]. Although XIST is not normally expressed in XY cells, these studies suggest that aberrant regulation of this lncRNA can occur in both male and female tumors.…”

Section: Sex Differences In Epigeneticsmentioning

confidence: 82%

Sex differences in cancer mechanisms

et al. 2020

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We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab-and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.

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Section: Sex Differences In Epigeneticsmentioning

confidence: 82%

Sex differences in cancer mechanisms

et al. 2020

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“…It has been well documented that lncRNA XIST acts as an oncogenic factor, driving the formation and growth of cancer cells, promoting the epithelial–mesenchymal transition, and indicating poor prognosis in human cancers 19–21. However, little is known about its role in the polarization of tumor-associated macrophages, an important cellular program during tumor progression 22.…”

Section: Discussionmentioning

confidence: 99%

<p>TCF-4 Regulated lncRNA-XIST Promotes M2 Polarization Of Macrophages And Is Associated With Lung Cancer</p>

Sun¹,

Xu²

2019

OTT

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BackgroundLittle is known about the biological function of long non-coding RNA X inactive specific transcript (lncRNA XIST) and its underlying mechanism in tumor-associated macrophage (TAM) polarization of lung cancer.Materials and methodsThe expression of lncRNA XIST in macrophages was detected by RT-qPCR. The function of lncRNA XIST on IL-4-induced M2 polarization was evaluated by transfection of shRNA and RT-qPCR or Western blotting detection of M2 specific markers. Contact between T-cell-specific transcription factor 4 (TCF-4) and lncRNA XIST was verified by bioinformatics and luciferase assay. The relation between lncRNA XIST and lung cancer was determined by bioinformatics.ResultsThe expression of lncRNA XIST in THP-1-differentiated macrophages was significantly increased in M2 macrophages than M1 (P < 0.05). lncRNA XIST downregulation suppressed the IL-4-induced M2 polarization, inducing downregulation of M2 specific markers such as IL-10, Arg-1, and CD163. However, the suppression was aborted by overexpression of TCF-4. Mechanistically, lncRNA XIST was regulated by TCF-4 through direct binding. Additionally, lung cancer conditioned macrophages exhibited high expression of lncRNA XIST and lung cancer tissues highly expressed TCF-4, indicating TCF-4 regulated lncRNA XIST closely correlated with macrophage polarization and tumor progression of lung cancer.ConclusionTaken together, this study demonstrated the important role of TCF-4 regulated lncRNA XIST in regulating M2 polarization and gave a novel insight into the TAMs regulation and potential therapeutic target of lung cancer.

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“…Growing evidence from recent studies has shown that lncRNA Xist facilitates tumor development, including pituitary neuroendocrine tumor, neuroblastoma, thyroid cancer, colon cancer, renal cell carcinoma, and prostate cancer ( Chaligne and Heard, 2014 ; Yang Z. et al, 2018 ; Liu et al, 2019c ). In the pituitary neuroendocrine tumor cells ( Zhou et al, 2019b ), lncRNA Xist, which functions as a ceRNA to sequester miR-424-5p to elevate the expression of the its target bFGF, and exhibits high expression in invasive pituitary neuroendocrine tumor tissues as compared to non-invasive tumor tissues, promotes cancer progression in invasive pituitary neuroendocrine tumor via activating the miR-424-5p/bFGF signaling pathway.…”

Section: The Role Of Lncrna Xist In Cancermentioning

confidence: 99%

Biological Function of Long Non-coding RNA (LncRNA) Xist

Wang

Min

Guo

et al. 2021

Front. Cell Dev. Biol.

139

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Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (Furlan and Rougeulle, 2016; Maduro et al., 2016). These RNAs are believed to be transcribed by the approximately 98–99% non-coding regions of the human genome (Derrien et al., 2012; Fu, 2014; Montalbano et al., 2017; Slack and Chinnaiyan, 2019), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (Ma et al., 2013; Devaux et al., 2015; St Laurent et al., 2015; Chen, 2016; Quinn and Chang, 2016; Richard and Eichhorn, 2018; Connerty et al., 2020). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (Cao et al., 2018). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (Jiang W. et al., 2018; Zhou et al., 2019a). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000–20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (Brown et al., 1992; Debrand et al., 1998; Kay, 1998; Lee et al., 2013; da Rocha and Heard, 2017; Yang Z. et al., 2018; Brockdorff, 2019). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (Liu et al., 2018b; Deng et al., 2019; Dinescu et al., 2019; Mutzel and Schulz, 2020; Patrat et al., 2020; Wang et al., 2020a). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in Table 1. It was also believed that lncRNA Xist (Chaligne and Heard, 2014; Yang Z. et al., 2018) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in Table 2. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease.

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Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers

Cited by 15 publications

References 26 publications

Sex differences in cancer mechanisms

Sex differences in cancer mechanisms

<p>TCF-4 Regulated lncRNA-XIST Promotes M2 Polarization Of Macrophages And Is Associated With Lung Cancer</p>

Biological Function of Long Non-coding RNA (LncRNA) Xist

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