X-inactive Specific Transcript Research Articles

Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1.

Long noncoding RNAs (lncRNAs) have been reported to take part in intracellular RNA regulatory networks and play important roles in a lot of pathological processes. Currently, lncRNA X-inactive specific transcript (XIST) has been proved to regulate cell migration, proliferation, and apoptosis in a series of cancers. In this study, we explored whether XIST can affect cell proliferation, migration, and apoptosis in bladder cancer. The influences of XIST on the cell proliferation, cell cycle, and apoptosis were detected in bladder cancer cells. The effect of XIST on the migration of bladder cancer cells was examined by cell migration assay. Through RNA immunoprecipitation and chromatin immunoprecipitation assays, the binding relationship between XIST and TET1 and the regulatory mechanism of TET1 on p53 were examined. Western blot was performed to detect p53 after knockdown or overexpression of XIST. We found that knockdown of XIST suppressed cell migration and proliferation in vitro. Mechanistically, we confirmed that lncRNA XIST participates in bladder cancer by downregulating p53 via binding to TET1. In conclusion, our research revealed the potential role of XIST-TET1-p53 regulatory network in bladder cancer.

LncRNA XIST mediates bovine mammary epithelial cell inflammatory response via NF-κB/NLRP3 inflammasome pathway.

ObjectivesThe correlations between long non‐coding RNAs (lncRNAs) and diverse mammal diseases have been clarified by many researches, but the cognition about bovine mastitis‐related lncRNAs remains limited. This study aimed to investigate the potential role of lncRNA X‐inactive specific transcript (XIST) in the inflammatory response of bovine mammary epithelial cells.Materials and methodsTwo inflammatory bovine mammary alveolar cell‐T (MAC‐T) models were established by infecting the cells with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The expressions of pro‐inflammatory cytokines were measured, and the proliferation, viability and apoptosis of the inflammatory cells were evaluated after XIST was knocked down by an siRNA. The relationship among XIST, NF‐κB pathway and NOD‐like receptor protein 3 (NLRP3) inflammasome was investigated using an inhibitor of NF‐κB signal pathway.ResultsThe expression of XIST was abnormally increased in bovine mastitic tissues and inflammatory MAC‐T cells. Silencing of XIST significantly increased the expression of E. coli or S. aureus‐induced pro‐inflammatory cytokines. Additionally, knockdown of XIST could inhibit cell proliferation, suppress cell viability and promote cell apoptosis under inflammatory conditions. Furthermore, XIST inhibited E. coli or S. aureus‐induced NF‐κB phosphorylation and the production of NLRP3 inflammasome.ConclusionsThe expression of XIST was promoted by activated NF‐κB pathway and, in turn, XIST generated a negative feedback loop to regulate NF‐κB/NLRP3 inflammasome pathway for mediating the process of inflammation.

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

Growing evidence from recent studies has shown that the X-inactive specific transcript (XIST), a well-known long noncoding RNA involved in early embryonic development, is aberrantly regulated in various human cancers. However, the prognostic value of XIST in cancers remains uncharacterized. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies, and a meta-analysis was performed to explore the association of XIST expression with overall survival (OS) and clinicopathological parameters. We demonstrated that high XIST expression was associated with poor OS (hazard ratio = 1.76; 95% confidence intervals [CI], 1.56-1.98; p < 0.001). In addition, increased XIST expression was found to be associated with lymph node metastasis (odds ratio [OR] = 2.06; 95% CI, 1.46-1.90; p < 0.001), distant metastasis (OR = 2.93; 95% CI, 2.00-4.28; p < 0.001), tumor size (OR = 2.66; 95% CI, 1.86-3.81; p < 0.001), poor differentiation (OR = 1.45; 95% CI, 1.00-2.10; p = 0.049), and advanced tumor stage (OR = 3.35; 95% CI, 2.25-5.00; p < 0.001), but not with age (OR = 0.82; 95% CI, 0.59-1.15; p = 0.251) or gender (OR = 0.92; 95% CI, 0.70-1.19; p = 0.512). Our meta-analysis showed that XIST may be a useful common biomarker for predicting prognosis in patients with cancer.

LncRNA X inactive specific transcript contributes to neuropathic pain development by sponging miR-154-5p via inducing toll-like receptor 5 in CCI rat models.

Noncoding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs, are involved in the development of neuropathic pain. Currently, we investigated that lncRNA X inactive-specific transcript (XIST) and toll-like receptor 5 (TLR5) were greatly upregulated in chronic constriction injury rat models, whereas miR-154-5p (microRNA-154-5p) was significantly downregulated. Bioinformatics analysis was used to predict miR-154-5p as a target gene of XIST, and dual-luciferase reporter tests proved the correlation between them. We observed that miR-154-5p was negatively modulated by XIST in vitro. XIST overexpression markedly induced neuropathic pain development in rats with chronic constriction injury, whereas the upregulation of miR-154-5p could reverse this phenomenon. Furthermore, TLR5 was demonstrated to be a target gene of miR-154-5p by using bioinformatics predictions. miR-154-5p negatively regulated TLR5 expression in vitro, and TLR5 was able to promote neuropathic pain development. In addition, overexpressing miR-154-5p can reverse the role of TLR5 neuropathic pain in vivo. Taken these together, we indicated that XIST could increase TLR5 expression by acting as a sponge of miR-154-5p in neuropathic pain development. This study revealed that XIST can contribute to neuropathic pain progression in rats through decreasing miR-154-5p and increasing TLR5. The XIST/miR-154-5p/ TLR5 axis can be provided as a novel therapeutic target in treating neuropathic pain.

Long non-coding RNA XIST predicts poor prognosis and promotes malignant phenotypes in osteosarcoma.

Increasing evidence indicates that long non-coding RNA (lncRNA) is involved in a number of types of human cancer and functions as an oncogene or tumor suppressor. However, little is known about the role of lncRNA X-inactive specific transcript (XIST) in osteosarcoma. In the present study, the expression of lncRNA XIST was analyzed in 56 osteosarcoma tissues and their corresponding normal bone tissues by reverse transcription-quantitative polymerase chain reaction. Increased lncRNA XIST expression was observed in osteosarcoma tissues compared with the normal tissues and was positively associated with advanced Enneking stage. In addition, lncRNA XIST may be used as an independent risk factor for the overall survival of patients with osteosarcoma. Knockdown of lncRNA XIST inhibited cell proliferation, induced cell apoptosis and arrested the cell cycle. The inhibition of lncRNA XIST may also suppress cell migration and invasion in vitro. The present study suggested that lncRNA XIST acted as an oncogene in osteosarcoma, which may make it a novel therapeutic target for the treatment of osteosarcoma.

The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR-330-3p

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in numerous kinds of cardiovascular diseases, and their vital role in regulating cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA X-inactive specific transcript (XIST) was upregulated in hypertrophic cardiac of mice and phenylephrine (PE)-treated cardiomyocytes. Next, we observed that inhibition of XIST induced hypertrophic response of cardiomyocyte and overexpression of XIST attenuated cardiomyocyte hypertrophy induced by PE. Furthermore, through online predictive tools and functional experiments, we demonstrated that XIST and S100B were targets of miR-330-3p. XIST and miR-330-3p suppressed each other in a reciprocal way in cardiomyocytes. Additionally, XIST promoted S100B expression through harboring the complementary binding sites with miR-330-3p, eventually prevented cardiac hypertrophy. In conclusion, our findings revealed a novel molecular mechanism that XIST/miR-330-3p/S100B pathway modulates the progression of cardiomyocyte hypertrophy.

The TGF-β-regulated X-inactive specific transcript inhibits papillary thyroid cancer migration and invasion

Background: As a common endocrine gland malignancy worldwide, papillary thyroid cancer (PTC) shows a relatively high survival of PTC patients, but their prognosis becomes worse as soon as the lymph nodes are invaded. In our study, we found that a long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) was associated with lymph node metastasis in PTC. Our purpose was to explore the functions and underlying mechanisms of this lncRNA in PTC. Methods: Bioinformatics analyses were performed with data from The Cancer Genome Atlas (TCGA) database. We confirmed the results in PTC tissues using quantitative real time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), and then studied the functions using Transwell® invasion and migration assays in vitro with TPC-1 and BCPAP cells. The correlation between XIST and the TGF-β pathway was confirmed using qRT-PCR and western blotting of PTC cell samples. All data were analyzed with SPSS software. Results: Using bioinformatics analyses and RNA detection techniques, we found that lncRNA XIST was associated with lymph node metastasis in PTC. The in vitro assays showed that XIST inhibited PTC cell invasion and migration. Furthermore, we found that XIST expression was correlated with Smad4, a core protein in the TGF-β pathway. Through co-transfection assays in PTC cells, we showed that XIST expression was inhibited by TGF-β, and this promoted PTC cell invasion and migration. Conclusions: We found that lncRNA XIST functioned as an inhibitor of PTC metastasis. Furthermore, TGF-β suppressed the expression of this lncRNA in PTC cells. As XIST is regulated by TGF-β and functions as an inhibitor of PTC metastasis, it may serve as a new biomarker of PTC patient metastasis and prognosis.

Long noncoding RNA XIST promotes proliferation and invasion by targeting miR-141 in papillary thyroid carcinoma.

BackgroundThe long noncoding RNA X-inactive specific transcript (XIST) was reported to play vital roles in tumor progression. In the present study, we determined the regulatory function of XIST in papillary thyroid carcinoma (PTC).Materials and methodsXIST expression was determined in PTC tissues and cell lines by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). Cellular proliferation, migration, and invasion were measured using the Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and transwell invasion assay, respectively. Western blotting was used to determine protein expression. The downstream target miRNAs for XIST were identified by luciferase reporter assay and qRT-PCR.ResultsRelative expression of XIST was upregulated in PTC tissues and cell lines. High XIST expression was positively correlated with TNM stage and lymph node metastasis. Function assay demonstrated that knockdown of XIST significantly decreased cell proliferation, migration, and invasion in PTC cells. Moreover, we showed that the effects of XIST on PTC cell progression were mediated by miR-141.ConclusionOur results demonstrated that XIST functioned as an oncogene in PTC progression by regulating miR-141, suggesting that XIST might be a promising therapeutic target for PTC treatment.

The TGF-β-regulated X-inactive specific transcript inhibits papillary thyroid cancer migration and invasion

The TGF-β-regulated X-inactive specific transcript inhibits papillary thyroid cancer migration and invasion

Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis.

Up to 30% of patients with metastatic breast cancer eventually develop brain metastasis, yet the pathologic mechanism behind this development remains poorly understood. Here, we profiled long noncoding RNAs in brain metastatic tumors from patients with breast cancer and found that the X-inactive-specific transcript (XIST) was significantly downregulated in these tissues. XIST expression levels inversely correlated with brain metastasis, but not with bone metastasis in patients. Silencing of XIST preferentially promoted brain metastatic growth of XISThigh cells in our xenograft models. Moreover, knockout of XIST in mice mammary glands accelerated primary tumor growth as well as metastases in the brain. Decreased expression of XIST stimulated epithelial-mesenchymal transition and activated c-Met via MSN-mediated protein stabilization, which resulted in the promotion of stemness in the tumor cells. Loss of XIST also augmented secretion of exosomal miRNA-503, which triggered M1-M2 polarization of microglia. This M1-M2 conversion upregulated immune suppressive cytokines in microglia that suppressed T-cell proliferation. Furthermore, we screened an FDA-approved drug library and identified fludarabine as a synthetic lethal drug for XISTlow breast tumor cells and found that fludarabine blocked brain metastasis in our animal model. Our results indicate that XIST plays a critical role in brain metastasis in breast cancer by affecting both tumor cells and the tumor microenvironment and that the XIST-mediated pathway may serve as an effective target for treating brain metastasis.Significance: These findings describe mechanisms of how loss of the lncRNA XIST promotes brain metastasis in breast cancer and identify fludarabine as a potential therapeutic agent that specifically eliminates XISTlow tumor cells in the brain. Cancer Res; 78(15); 4316-30. ©2018 AACR.

Long Noncoding RNA XIST Promotes Osteosarcoma Progression by Targeting Ras-Related Protein RAP2B via miR-320b.

Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the unrestricted growth and invasion of cancer cells. lncRNA X-inactive specific transcript (XIST) expression is upregulated in several cancers; however, its underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present study, we found that XIST expression was significantly increased in OS tissues and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b on OS cell proliferation and invasion were studied by MTT and Transwell invasion assays. The competing relationship between XIST and miR-320b was confirmed by luciferase reporter assay. Our results showed that XIST knockdown strikingly inhibited cell proliferation and invasion. Furthermore, XIST could directly bind to miR-320b and repress miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression of Ras-related protein RAP2B. We propose that XIST is responsible for OS cell proliferation and invasion and that XIST exerts its function through the miR-320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in OS patients.

Long non-coding RNA XIST predicts worse prognosis in digestive system tumors: a systemic review and meta-analysis.

Increasing studies are indicating that long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focussed our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to 3 January 2018). Fifteen studies which matched our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR = 1.81, 95% CI: 1.45–2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR = 2.24, 95% CI: 1.73–2.92) than in non-digestive system tumors (pooled HR = 1.22, 95% CI: 0.60–2.45). Furthermore, elevated expression levels of XIST were connected with distant metastasis and tumor stage. XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors.

Knockdown of long noncoding RNA XIST alleviates oxidative low-density lipoprotein-mediated endothelial cells injury through modulation of miR-320/NOD2 axis

Atherosclerosis remains to be one of the most common vascular disorders resulting in morbidity and mortality in the world. Recent studies suggested that endothelial cells (ECs) injury caused by oxidative low-density lipoprotein (ox-LDL) is an early marker for atherosclerosis. Nevertheless, the mechanisms of ox-LDL-induced ECs injury are complicated and largely unknown. Here, we found lncRNA XIST (X-inactive specific transcript) was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL. Knockdown of XIST boosted the cell viability and suppressed cell apoptosis under ox-LDL stimuli. Further experiments identified XIST regulated the expression of Nucleotide-Binding Oligomerization Domain 2 (NOD2) by sponging miR-320. XIST silencing exerted a protective effect on ox-LDL-induced HUVECs injury via miR-320/NOD2 regulatory network. Our data provide insight into the role of the lncRNA XIST in ox-LDL mediated ECs injury, which can aid in developing new therapeutic strategies for the treatment of atherosclerosis.

Knockdown of LncRNA-XIST Suppresses Proliferation and TGF-β1-Induced EMT in NSCLC Through the Notch-1 Pathway by Regulation of miR-137.

Noncoding RNAs (ncRNAs), primarily microRNAs and long ncRNAs, play important roles in lung cancer. However, the role of long ncRNA (lncRNA)-X-inactive specific transcript (XIST) in non-small-cell lung cancer (NSCLC) is unclear. The purpose of this study was to explore the biologic function and potential mechanism of XIST in NSCLC progression. XIST, miR-137, and Notch-1 expression were detected by quantitative real-time PCR (qRT-PCR). Levels of proliferation- and epithelial-mesenchymal transition (EMT)-related proteins were assessed by Western blot. The correlations between XIST and miR-137, as well as miR-137 and Notch-1, were evaluated by bioinformatic analysis and luciferase reporter assays. We confirmed that XIST is aberrantly upregulated in NSCLC tissues and cell lines. XIST depletion inhibited cell proliferation and TGF-β1-induced EMT in A549 and H1299 cells. Spearman's correlation analysis showed an inverse correlation between miR-137 and XIST in NSCLC tissues, and miR-137 levels were found to be aberrantly reduced in A549 and H1299 cells. Furthermore, XIST could act as an endogenous sponge by directly binding to miR-137, negatively regulating its expression. miR-137 overexpression inhibited proliferation and TGF-β1-induced EMT in A549 and H1299 cells, whereas XIST could reverse the inhibitory effect of miR-137 on proliferation and TGF-β1-induced EMT. In addition, Notch-1 was identified as a direct target gene of miR-137, with the XIST-miR-137 axis regulating activation of the Notch-1 pathway. We identified a branch of the XIST/miR-137/Notch-1 pathway that regulates proliferation and TGF-β1-induced EMT in NSCLC, which could be involved in NSCLC progression.

MiR-34a-mediated regulation of XIST in female cells under inflammation.

BackgroundEvidence is overwhelming for sex differences in pain, with women representing the majority of the chronic pain patient population. There is a need to explore novel avenues to elucidate this sex bias in the development of chronic inflammatory pain conditions. Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder, and the incidence of CRPS is greater in women than in men by ~4:1. Since neurogenic inflammation is a key feature of CRPS, dysregulation of inflammatory responses can be a factor in predisposing women to chronic pain.MethodsOur studies investigating alterations in circulating microRNAs (miRNAs) in whole blood from female CRPS patients showed significant differential expression of miRNAs between responders and poor responders to ketamine treatment. Several of these miRNAs are predicted to target the long noncoding RNA, X-inactive-specific transcript (XIST). XIST mediates X-chromosome inactivation and is essential for equalizing the expression of X-linked genes between females and males. Based on the well-established role in inflammatory process, we focused on miR-34a, one of the miRNAs predicted to target XIST, and downregulated in CRPS patients responding poorly to ketamine.ResultsOur in vitro and in vivo models of acute inflammation and data from patients with CRPS showed that miR-34a can regulate XIST under inflammation directly, and through pro-inflammatory transcription factor Yin-Yang 1 (YY1). XIST was significantly upregulated in a subset of CRPS patients responding poorly to ketamine.ConclusionSince dysregulation of XIST can result in genes escaping inactivation or reactivation in female cells, further investigations on the role of XIST in the predominance of chronic inflammatory and pain disorders in women is warranted.

The eXceptional nature of the X chromosome.

The X chromosome is unique in the genome. In this review we discuss recent advances in our understanding of the genetics and epigenetics of the X chromosome. The X chromosome shares limited conservation with its ancestral homologue the Y chromosome and the resulting difference in X-chromosome dosage between males and females is largely compensated for by X-chromosome inactivation. The process of inactivation is initiated by the long non-coding RNA X-inactive specific transcript (XIST) and achieved through interaction with multiple synergistic silencing pathways. Identification of Xist-interacting proteins has given insight into these processes yet the cascade of events from initiation to maintenance have still to be resolved. In particular, the initiation of inactivation in humans has been challenging to study as: it occurs very early in development; most human embryonic stem cell lines already have an inactive X; and the process seems to differ from mouse. Another difference between human and mouse X inactivation is the larger number of human genes that escape silencing. In humans over 20% of X-linked genes continue to be expressed from the otherwise inactive X chromosome. We are only beginning to understand how such escape occurs but there is growing recognition that escapees contribute to sexually dimorphic traits. The unique biology and epigenetics of the X chromosome have often led to its exclusion from disease studies, yet the X constitutes 5% of the genome and is an important contributor to disease, often in a sex-specific manner.

The Long Non‐Coding RNA XIST Is Decreased in Lungs and Plasma Exosomes of Sickle Cell Mice and in Hemin‐Treated Human Pulmonary Artery Endothelial Cells

RationalePulmonaryhypertension (PH), a serious complication of sicklecell disease (SCD), causes significant morbidity andmortality. The release ofhemoglobin and free heme during hemolysis triggers endothelial dysfunction andcontributes to PH pathogenesis. Emerging evidence indicates that longnon‐coding RNAs (lncRNAs) play a pivotal role in cellular proliferation,differentiation, and apoptosis. Circulating exosomes, which are nano‐sized extracellular vesicles, contain lncRNAs and play an important role in intercellular communication. However, the role of lncRNAs released from lungs and plasmaexosomes in SCD‐PH pathogenesis has not been defined. We hypothesized that lncRNAs are differentially expressed in SSmouse lungs and plasma exosomes and in hemin‐treated human pulmonary artery endothelialcells (HPAECs).Methods and ResultslncRNAs were isolated from lungs and plasma exosomes of sicklecell (SS) mice and littermate control (AA) mice at age 15–17 weeks. Isolated plasma exosomes were characterized forlevels of exosomal markers (CD9, CD45, and CD63), following which exosomes andlung samples were subjected to determine theexpression profiles of 90 lncRNAs using the LncProfiler™ lncRNA qPCR array(System Bioscienes). 5 lncRNAs were increased and10 lncRNAs were decreased in the lungs and plasma exosomes of SS mice compared to AA mice. One of thelncRNAs found to be decreased in SS samples was X‐inactivespecific transcript (XIST). To further examinewhether hemin reduces lncRNA XIST expression, HPAECs were treated with DMSO or hemin (5 uM) for 72 hours. XIST expression was decreased in hemin‐treatedHPAECs. Hemin also stimulated dose (0–10 μM)− and time (0–72hours)‐dependent increases in HPAEC monocyteadhesion and proliferation (BrdU assays). Because PPAR gamma (PPARg) levels were reduced in the lungs of SS mice,and pharmacological PPARg activation attenuated SCD‐PH, we examined the impactof PPARg activation on XIST levels in SS mouse lungs and found that PPARgactivation attenuates reductions in XIST expression.ConclusionsTheseresults suggest that sickle cell disease can impact lncRNAs and these effectsmay be reversed by treatment with PPARg agonists. Therefore, characterizationof lncRNAs are impacted in SCD may provide new insights into SCD pulmonaryvascular dysfunction and PH pathogenesis and identify novel targets fortherapeutic intervention.Support or Funding InformationSupported by NIH HL102167 (RLS and CMH) and NIH HL133053‐01A1 (BYK).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long non-coding RNA XIST promotes osteosarcoma progression by targeting YAP via miR-195-5p.

The lncRNA XIST (X inactive-specific transcript) is an oncogenic lncRNA that is present in various malignant tumors; however, its role and molecular mechanisms in osteosarcoma (OS) progression remain unclear. In the current study, 40 pairs of OS tissues and matched adjacent non-tumor tissues were collected. qRT-PCR was conducted to investigate the differences in XIST expression in tissues and OS cell lines. The proliferation, invasion, and EMT status of OS cells after transfection were assessed with WST-1 assays, Transwell assays, and Western blot analysis, respectively. Whether miR-195-5p was a direct downstream target of XIST was verified by both bioinformatics target gene prediction and dual-luciferase report analysis. A mouse model was established to evaluate tumor proliferation in vivo. Our results demonstrated that XIST expression was significantly upregulated in OS tissues and cell lines and negatively correlated with clinical prognosis. XIST knockdown inhibited cancer cell proliferation and invasion in vitro, inhibited the EMT of OS cells in vitro, and suppressed subcutaneous tumor growth in vivo. Further analysis demonstrated that XIST regulated YAP expression by functioning as a competing endogenous RNA that sponged miR-195-5p in OS cells. XIST directly interacted with miR-195-5p and decreased the binding of miR-195-5p to the YAP 3'UTR, which suppressed the degradation of YAP mRNA by miR-195-5p. In conclusion, this work demonstrates that lncRNA XIST enhances OS cancer cell proliferation and invasion in part through the miR-195-5p/YAP pathway. Therefore, lncRNA XIST might be a promising therapeutic target for OS.

LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells

BackgroundThe abnormal expression of non-coding RNAs (ncRNAs), such as microRNAs and long ncRNAs, often contribute to the development of cancers. miR-200c functions as a tumour suppressor that impacts the growth of bladder cancer cells and the epithelial-to-mesenchymal transition (EMT). LncRNA X inactive specific transcript (XIST) is highly expressed in tumour tissues, promotes cancer progression and might act as an miRNA molecular sponge. This study aimed to examine the relationship between lncRNA XIST and miR-200c and to assess their functions in the regulation of the stemness properties and tumourigenicity of human bladder cancer stem cell (BCSC)-like cells.MethodsBiological effects including cell clone formation, sphere formation, self-renewal properties and mouse tumourigenesis were examined in BCSC-like cells with miR-200c overexpression or XIST knockdown. Real-time PCR and western blotting were used to detect the expression changing of related factors in BCSC-like cells gene models. Dual luciferase reporter assay was used to examine the changes of XIST and miR-200c expression levels.ResultsThe results indicated that miR-200c overexpression and XIST knockdown could inhibit cell clone formation, self-renewal ability and EMT in BCSC-like cells. miR-200c knockdown could restore the tumour growth inhibition caused by XIST knockdown.ConclusionLncRNA XIST may act as an inhibitor of miR-200c to regulate the stemness properties and tumourigenicity of bladder cancer cells, and our findings might reveal a potential strategy of targeting XIST for bladder cancer therapy.

Long non-coding RNA XIST inhibited breast cancer cell growth, migration, and invasion via miR-155/CDX1 axis

Long non-coding RNA (lncRNA) is an important member of non-coding RNA family and emerging evidence has indicated that it plays a pivotal role in many physiological and pathological processes. The lncRNA X inactive specific transcript (XIST) is a potential tumour suppressor in some types of cancers. However, the expression and function of XIST in breast cancer remain largely unclear. The objective of this study was to evaluate the expression and biological role of XIST in breast cancer. The results showed that XIST was significantly down-regulated in breast cancer tissues and cell lines. Further functional analysis indicated that overexpression of XIST remarkably inhibited breast cancer cell growth, migration, and invasion. The results of luciferase reporter assays verified that miR-155 was a direct target of XIST in breast cancer. Moreover, caudal-type homeobox 1 (CDX1) was identified as a direct target of miR-155 and miR-155/CDX1 rescued the effects of XIST in breast cancer cells. Taken together, our results suggest that XIST is down-regulated in breast cancer and suppresses breast cancer cell growth, migration, and invasion via the miR-155/CDX1 axis.