Non-coding RNA X-inactive Specific Transcript Research Articles

Long Non-coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P/AHNAK/BMP2 Signaling Pathway.

Long non-coding RNAs (lncRNAs) play an important role in the development of bone-related diseases. This study was conducted to investigate the role and mechanism of lncRNA X inactive specific transcript (XIST) in the occurrence of cervical ossification of the posterior longitudinal ligament (OPLL). Here, primary human ligament fibroblasts cells (LFCs) were isolated from 30 cases of OPLL and 30 normal cervical posterior longitudinal ligament (non-OPLL) tissues to perform the qPCR and Western blot assay. We found that the mRNA level of lncRNA XIST was significantly increased in OPLL LFCs compared to non-OPLL LFCs. By bioinformatics analysis, we found that lncRNA XIST has four binding sites for miR-17-5p and found that the mRNA level of miR-17-5p was also significantly decreased in OPLL LFCs compared to non-OPLL LFCs. Since AHNAK is the target gene of miR-17-5p, we further found that the expression of AHNAK was significantly reduced in non-OPLL LFCs after being transfected with miR-17-5p mimic. The qPCR results showed that the mRNA expressions of BMP2 and Runx2 were significantly decreased. After being transfected with lncRNA XIST siRNA in the non-OPLL LFCs, the mRNA levels of lncRNA XIST, AHNAK, BMP2, and Runx2 were significantly decreased and the phosphorylated protein of Smad1/5/8 was reduced. After being cultured by mechanical vibration, the mRNA levels of lncRNA XIST, AHNAK, BMP2, Runx2, COL1, OC, OPN, and Phospho1 were significantly increased, but the mRNA expression of miR-17-5p was significantly decreased. The expression of phosphorylated Smad1/5/8 protein was also significantly increased. Together, this study was the first to determine that XIST gene inhibition plays an important role in the occurrence of cervical OPLL, through the mechanism of regulation of miR-17-5P/AHNAK/BMP2 signaling pathway. Thus, XIST may be a potential target that could be modulated for the treatment of cervical OPLL.

The suppression of ox-LDL-induced inflammatory response and apoptosis of HUVEC by lncRNA XIAT knockdown via regulating miR-30c-5p/PTEN axis.

Exposure of oxidized low-density lipoprotein (ox-LDL) could cause dysfunction of HUVEC, thus leading to atherosclerosis development, which is a common inflammatory vascular disease. Long noncoding RNA X-inactive specific transcript (XIST) has been reported to be implicated in atherosclerosis. However, the mechanism by which this lncRNA participates in the progression of atherosclerosis is poorly defined. HUVEC challenged by ox-LDL were used as a cellular model of atherosclerosis. Cell viability, apoptosis, LDH release, and inflammatory cytokines secretion were detected by MTT, flow cytometry, and ELISA assays. The expression levels of XIST, microRNA (miR)-30c-5p, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured by quantitative Real Time-Polymerase Chain Reaction and Western blot. The target interaction between XIST and miR-30c-5p or miR-30c-5p and PTEN was validated by the Luciferase reporter assay and RNA immunoprecipitation. Treatment of ox-LDL induced cell apoptosis and inflammatory cytokines release in HUVEC. XIST expression was enhanced in HUVEC treated by ox-LDL, and its knockdown decreased cell apoptosis and inflammatory response in ox-LDL-treated cells. MiR-30c-5p was a target of XIST and its overexpression suppressed cell apoptosis and inflammatory response induced by ox-LDL, which was weakened by the introduction of XIST. PTEN was a target of miR-30c-5p, and its interference led to great inhibition of cell apoptosis and inflammatory response induced by ox-LDL in HUVEC, while this effect was attenuated by miR-30c-5p deficiency or XIST overexpression. XIST knockdown suppresses inflammatory response and apoptosis of HUVEC stimulated by ox-LDL by increasing miR-30c-5p and decreasing PTEN.

Long Non-Coding RNA (lncRNA) X-Inactive Specific Transcript (XIST) Plays a Critical Role in Predicting Clinical Prognosis and Progression of Colorectal Cancer.

BackgroundLong non-coding RNAs (lncRNAs) participate in all cancer biology processes of cells. Although functions and associated mechanisms of lncRNAs have been proven in colorectal cancer (CRC), the roles of lncRNA X-inactive specific transcript (XIST) have not been clearly investigated in CRC.Material/MethodsExpression of XIST was detected by quantitative real-time PCR (qRT-PCR) assay in CRC cell lines and 196 clinical samples. Correlations between XIST expression and CRC clinicopathological features were analyzed. Log-rank test and Kaplan-Meier test were performed to assess and compare the prognoses of patients with higher and lower expression of XIST. The multivariate Cox regression and univariate Cox regression were conducted to evaluate the risk factors for prognosis of CRC.ResultslncRNA XIST was upregulated in CRC cells lines and tissues (p<0.05). Statistical analysis found high XIST expression was correlated with larger tumor size, N1, M1, and topography lymph node metastasis (TNM) III+IV stage of CRC. Moreover, higher expression of XIST could predict poor progression-free survival (PFS) and poor overall survival (OS) of CRC patients. The M1 stage and high expression of XIST were proven to be independent risk factors for poor prognosis (p<0.05).ConclusionsXIST is upregulated in CRC and is significantly correlated with CRC clinical progression. lncRNA XIST overexpression predict poor PFS and poor OS for CRC patients. lncRNA XIST can be an independent risk factor for CRC prognosis, and could be a potential therapeutic target and prognostic biomarker for CRC patients.

Long non-coding RNA XIST predicting advanced clinical parameters in cancer: A Meta-Analysis and case series study in a single institution.

Dysregulated expression of long non-coding RNA X-inactive specific transcript (lncRNA-XIST) has been indicated in various cancer types. In the present study, a meta-analysis was conducted to evaluate the potential role of lncRNA-XIST in predicting the clinicopathological parameters of patients with cancer. Eligible studies were obtained through a systematic search of PubMed, Web of Science, Embase and the Cochrane Library, of articles published prior to January 2019. The combined odds ratio and 95% confidence interval were calculated to determine the association between lncRNA-XIST expression and patient outcome. In addition, 45 pairs of osteosarcoma (OS) tissues and adjacent healthy tissues from a single institution were analyzed for the expression of lncRNA-XIST, and its association with clinicopathological features; ultimately, a total of 1,869 cancer patients from 25 studies were assessed. The results demonstrated that high expression levels of lncRNA-XIST were significantly associated with lymphatic metastasis, larger tumor size, advanced cancer stage and distant metastasis. However, sex was not associated with lncRNA-XIST expression level. In the OS patient cohort, it was demonstrated that lncRNA-XIST was highly expressed in OS tissues, which negatively correlated with patient prognosis. The present study indicated that lncRNA-XIST may serve as a potential biomarker for advanced clinical parameters in human cancer.

LncRNA XIST enhanced TGF-β2 expression by targeting miR-141-3p to promote pancreatic cancer cells invasion

The level of expression of long non-coding RNA (LncRNA) X-inactive specific transcript (XIST) is up-regulated in pancreatic cancer (PC). However, the role of XIST in PC and the underlying mechanism are still unknown. The present study aimed to elucidate how XIST participates in PC and its potential target, miR-141-3p. We detected the XIST expression in PC tissues and cells by qRT-PCR. Cell proliferation was measured using a CCK8 kit, and the migration and invasion of cells was measured by Transwell assay. Silencing XIST and miR-141-3p was performed with transfection by Lipofectamine kit. Binding assay was conducted by luciferase reporter assay. Protein expression was examined by Western blot. These results indicate that (i) XIST is highly expressed in tumor tissues while miR-141-3p is down-regulated. (ii) Silencing XIST inhibits the pancreatic cell proliferation, migration and invasion. (iii) MiR-141-3p inhibitor alleviates the inhibitory effect by siXIST in PC cell lines. (iv) MiR-141-3p directly interacts with XIST and also negatively regulates transforming growth factor-β 2 (TGF-β2) expression. (v) Overexpression of XIST attenuates the inhibition of TGF-β2 expression by miR-141-3p. The conclusion, is that XIST could promote proliferation, migration and invasion of PC cells via miR-141-5p/TGF-β2 axis.

Long non-coding RNA XIST promotes extracellular matrix degradation by functioning as a competing endogenous RNA of miR-1277-5p in osteoarthritis.

Osteoarthritis (OA) is a common and troublesome disease among the elderly, and is characterized by extracellular matrix (ECM) degradation. The function of the long non-coding RNA X-inactive-specific transcript (XIST) and its working mechanism in ECM degradation remains unclear. In the present study, XIST was revealed to be upregulated in OA specimens and in articular chondrocytes (ACs) derived from OA tissue (AC/OA) and interleukin-1β (IL-1β)-treated ACs. Loss-of-function experiments demonstrated that downregulation of XIST suppressed the degradation of the ECM in AC/OA and AC/IL-1β-5.0 cells. Furthermore, XIST, matrix metalloproteinase 13 (MMP-13) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) were identified as targets of microRNA (miR)-1277-5p, and the reciprocal inhibitive effect between XIST and miR-1277-5p was elucidated. Furthermore, the role of XIST in ECM degradation was confirmed to be functioning as a competing endogenous RNA (ceRNA) of miR-1277-5p. Finally, the protective effect of the downregulation of XIST on ECM degradation was verified in an OA rat model. In conclusion, the present study suggests that XIST promotes MMP-13 and ADAMTS5 expression, indicating ECM degradation, by functioning as a ceRNA of miR-1277-5p in OA. The present study proposed a novel potential target with a new working mechanism in molecular treating of OA.

Long noncoding RNA X-inactive specific transcript promotes malignant melanoma progression and oxaliplatin resistance.

Long noncoding RNA X-inactive specific transcript (XIST) was confirmed to participate in the development of many cancers. However, the function of XIST in malignant melanoma (MM) remained largely unknown. In the current study, we found that the XIST expression level was upregulated in MM tissues and cell lines. In addition, the growth rate of MM cells transfected with silencing XIST was significantly decreased compared with that with silencing normal control. XIST knockdown inhibited proliferation and migration in MM cells and increased the oxaliplatin sensitivity of oxaliplatin-resistant MM cells. Bioinformatics analysis showed that XIST acts as a molecular sponge for miR-21 and miR-21 directly targets with 3'-UTR of PI3KR1. Furthermore, XIST knockdown inhibited PI3KRI and AKT expression, and promoted Bcl-2 and Bax expression. In short, the current study showed that XIST was a crucial regulator in progression and oxaliplatin resistance of MM, providing a novel insight into the pathogenesis and underlying therapeutic target for MM.

Long noncoding RNA XIST regulates the EGF receptor to promote TGF-β1-induced epithelial-mesenchymal transition in pancreatic cancer.

This study focuses on the lncRNA XIST (X inactive-specific transcript), an lncRNA involved in multiple human cancers, and investigates the functional significance of XIST and the molecular mechanisms underlying the epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC). Clinical specimens from 25 patients as well as 5 human PC cell lines were analyzed for XIST, YAP, and microRNA(miR)-34a by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. To investigate how XIST influences cell proliferation, invasiveness, and apoptosis in PC, we performed the CCK-8 assays, Transwell assays, and flow cytometry. Luciferase reporter assays, qRT-PCR, and Western blot were applied to prove that miR-34a directly binds to XIST. Up-regulation of XIST and Yes associated protein (YAP) and down-regulation of miR-34a were consistently observed in the clinical specimens and PC cell lines. Silencing XIST reduced the expression of YAP and suppressed transforming growth factor (TGF)-β1-induced EMT, while over-expression of XIST increased the expression of YAP and promoted EMT. In addition, inhibition of epidermal growth factor receptor (EGFR) hampered the XIST-promoted EMT. The results from the luciferase reporter assays confirmed that miR-34a directly targets XIST and suggested that XIST regulates cell proliferation, invasiveness, and apoptosis in PC by sponging miR-34a. XIST promotes TGF-β1-induced EMT by regulating the miR-34a-YAP-EGFR axis in PC.

Long non-coding RNA XIST regulates miR-106b-5p/P21 axis to suppress tumor progression in renal cell carcinoma

Long non-coding RNAs (lncRNAs) have been demonstrated to exert important roles in cancer development and progression. The biological function of lncRNA X-inactive specific transcript (XIST) in the development of renal cell carcinoma (RCC) and the underlying mechanisms are still largely unknown. In this study, we found that XIST was down-regulated in RCC tissues and cells. Overexpression of XIST significantly suppressed cell proliferation and induced cell G0/G1 arrest in vitro and inhibited tumor growth in vivo. We further found that XIST could directly interact with miR-106b-5p and increase the expression of P21. Thus, XIST positively regulated the expression of P21 through sponging miR-106b-5p, and played a tumor suppressor role in RCC. Moreover, we found that curcumin could regulate XIST/miR-106b-5p/P21 axis in RCC cells. Our study exhibits the role of XIST as a miRNA sponge in RCC and supports the potential application of XIST in RCC therapy.

LncRNA XIST facilitates proliferation and epithelial-mesenchymal transition of colorectal cancer cells through targeting miR-486-5p and promoting neuropilin-2.

This study was designed to acertain whether the long noncoding RNA (lncRNA) X-inactive specific transcript (XIST)/miR-486-5p/neuropilin-2 (NRP-2) pathway might promote theviability and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells. In this investigation, we included 317 pathologically confirmed CRC patients and purchased several human CRC cells (i.e. HCT116, HT29, SW620, and SW480). Moreover, pcDNA3.1-XIST, si-XIST, miR-486-5p mimic, miR-486-5p inhibitor, and pcDNA3.1-NRP-2 weretransfected into the CRC cells. And the dual-luciferase reporter gene assay managed to verify the targeted relationships among XIST, miR-486-5p, and NRP-2. Ultimately, the MTT assay, flow cytometry, colony formation assay, and transwell assay were carried out to assess the influence of XIST, miR-486-5p, and NRP-2 on the proliferation, apoptosis, migration, and invasion of CRC cells. Our study results demonstrated that CRC tissues and cells were detected with significantly elevated XIST and NRP-2 expressions as well as markedly reduced miR-486-5p expression when compared with normal tissues and cells (all p < 0.05). Besides this, the highly expressed XIST and NRP-2, as well as the lowly expressed miR-486-5p all could substantially encourage proliferation and EMT of CRC cells and simultaneously restrict apoptosis of the cells ( p < 0.05). Moreover, XIST was found to directly target miR-486-5p, and NRP-2 was directly targeted and modulated by miR-486-5p. Finally, CRC cells of the miR-NC + pcDNA3.1-NRP-2 groups showed stronger proliferation, viability, and EMT than those of miR-NC and miR-486-5p mimic groups ( p < 0.05). In conclusion, the XIST/miR-486 -5p/NRP-2 axis appeared to participate in the progression of CRC, which could assist in developing efficacious therapies for CRC.

The long noncoding RNA XIST regulates cardiac hypertrophy by targeting miR-101.

Cardiac hypertrophy and its resultant heart failure are among the most common causes of mortality, worldwide. Long noncoding RNAs (lncRNAs) are involved in diverse biological processes, and their vital role in the regulation of cardiac hypertrophy is increasingly being discovered. Nevertheless, the biological roles of lncRNA X-inactive specific transcript (XIST) in cardiac hypertrophy are scarcely reported, and the current study was designed to determine whether cardiac hypertrophy can be regulated by XIST and to elucidate the related mechanism. The animals were randomized to receive either an adeno-associated virus expressing XIST or control plasmid via a single bolus-tail vein injection. Two weeks later, hypertrophy was established by transverse aortic constriction (TAC) surgery. In vitro, H9c2 cells were used to explore the potential molecular mechanism of XIST in the regulation of phenylephrine (PE)-induced cardiomyocyte hypertrophy. A luciferase reporter assay and RNA immunoprecipitation were performed to explore the relationships among XIST, microRNA (miR)-101, and toll-like receptor 2 (TLR2). In this study, we demonstrated that the expression of XIST was significantly upregulated in hypertrophic mouse hearts and PE-treated cardiomyocytes. Then, we observed that knockdown of XIST attenuated PE-induced cardiomyocyte hypertrophy. Conversely, overexpression of XIST aggravated TAC-induced cardiac hypertrophy. Finally, we demonstrated that miR-101 was a direct target of XIST, whereas TLR2 was a target of miR-101. Rescue assays further confirmed that XIST promoted the progression of cardiac hypertrophy through competitively binding with miR-101 to enhance the expression of TLR2. Collectively, these in vivo and in vitro findings identify XIST as a necessary regulator of cardiac hypertrophy due to its regulation of the miR-101/TLR2 axis, suggesting that XIST might act as a therapeutic target for the treatment of cardiac hypertrophy and heart failure.

Long noncoding RNA X-inactive specific transcript as a prognostic factor in cancer patients: A meta-analysis based on retrospective studies.

Background/aims:Emerging evidence showed the long noncoding RNA X-inactive specific transcript (lncRNA XIST) may play a crucial role in various cancers. However, its prognostic value in cancer patients remains controversial. Therefore, we performed an in-depth meta-analysis to investigate the potential clinical value of lncRNA XIST as a prognostic marker for cancer patients.Methods:A comprehensive literature search was performed from PubMed, Embase and the Cochrane Central Search Library by January 2018. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% Cl) were calculated to evaluate the prognosis as well as clinicopathological parameters of XIST, respectively.Results:A total of 18 retrospective studies with 1351 cancer patients were included. Current meta-analysis revealed that elevated lncRNA XIST expression was associated with poor overall survival (OS) (HR = 2.14, 95% CI = 1.26–3.64; P = .005) and disease free survival (DFS) (HR = 4.52, 95% CI = 1.42–14.37; P = .011). The clinicopathological parameters analysis demonstrated that increased XIST expression was significantly associated with tumor size (OR = 2.93, 95% CI = 2.24–3.84; P < .001), clinical stage (OR = 2.73, 95% CI = 1.62–4.58; P < .001) and lymph node metastasis (OR = 2.44, 95% CI = 1.74–3.42; P < .001). In addition, subgroup analysis based on cancer type revealed that lncRNA XIST expression correlated with distant metastasis in digestive cancer (OR = 2.90, 95% CI = 1.80–4.68; P < .001).Conclusion:The current meta-analysis results indicated lncRNA XIST expression level could serve as a prognostic predictor and biomarker in multiple cancers.

Targeting XIST induced apoptosis of human osteosarcoma cells by activation of NF-kB/PUMA signal

ABSTRACT The long noncoding RNA X-inactive specific transcript (XIST) plays vital roles in tumor progression. However, the underlying mechanisms remain unclear. This study investigated the effects and mechanisms of targeting XIST on osteosarcoma (OS) cells in vitro and in vivo. We used shRNA to knockdown XIST to evaluate cell growth and apoptosis in U2OS cells in vitro and xenograft formation in vivo. An observed relationship between XIST and the p53 upregulated modulator of apoptosis (PUMA) and nuclear factor-kappa B (NF-kB) pathway was further explored by using small interfering RNA (siRNA). Our results showed that suppression of XIST by short hairpin RNA (shRNA) impeded U2OS cell growth, induced apoptosis and lessened OS xenograft tumor growth. Targeting XIST increased NF-kB-dependent PUMA upregulation in U2OS cells. Upregulation of PUMA is correlated with suppression of XIST-induced apoptosis in U2OS cells. Therefore, inhibition of XIST could promote U2OS cell death via activation of NF-kB/PUMA pathways.

Long Noncoding RNA XIST Binding to Let-7c-5p Contributes to Rheumatoid Arthritis Through Its Effects on Proliferation and Differentiation of Osteoblasts &lt;i&gt;via &lt;/i&gt;Regulation of STAT3

Rheumatoid arthritis (RA), a chronic autoimmune disease, affects around 1% population worldwide, with the life quality of patients severely reduced. In this study, we test the hypothesis that silencing long non-coding RNA x-inactive specific transcript (lncRNA XIST) acts as a biomarker for RA treatment through its effects on proliferation and differentiation of osteoblasts via let-7c-5p-mediated signal transducer and activator of transcription 3 (STAT3). We collected RA and normal cartilage tissues for determination of lncRNA XIST, let-7c-5p, and STAT3, the relationship among which were verified through alternation of lncRNA XIST and let-7c-5p in osteoblasts. The regulatory effects of lncRNA XIST in RA were investigated via loss-of-function and gain-of-function experiments. After RA rat models were established, TNF-α, IL-2, IL-6, alkaline phosphatase (ALP), osteocalcin, TGF-β1, and IGF1 were measured, and the damage degree of cartilage tissues was observed. The findings indicated that lncRNA XIST and STAT3 were highly expressed and let-7c-5p was reciprocal in RA cartilage tissues. LncRNA XIST knockdown or upregulation of let-7c-5p decreased levels of TNF-α, IL-2 and IL-6 to suppress inflammatory response, increased levels of ALP, osteocalcin, TGF-β1, and IGF-1 to promote proliferation and differentiation, and ameliorated pathological state and damage degree of cartilage tissues. these findings indicate that lncRNA XIST may act as a molecular sponge to regulate let-7c-5p, and its downregulation could relieve RA due to promoting effects on proliferation and differentiation of osteoblasts by inhibiting STAT3, serving as a future therapeutic strategy for RA. Funding Statement: This study was supported by grants from National Natural Science Foundation of China (No. 81402936; No.81302576), Six Talent Peak Research Project in Jiangsu Province (No. 2015-WSN-105), the 333 Project of Jiangsu Province, Jiangsu Province Youth Medical Talent Project, Jiangsu Provincial Natural Science Foundation of China (No. BK20131234). Declaration of Interests: The authors declare that we have no conflicts of interest. Ethics Approval Statement: All animal experiments were performed in line with the Guide for the Care and Use of Laboratory Animal. This study was approved by the Ethics Committee of Clinical Medical College, Yangzhou University, while all patients had provided the signed forms of informed consent.

Long Noncoding RNA XIST Regulates miR-137‐EZH2 Axis to Promote Tumor Metastasis in Colorectal Cancer

We aimed to investigate the significant role of long noncoding RNA X inactive specific transcript (XIST) in regulating tumor metastasis in colorectal cancer (CRC), as well as its possible mechanism. Expression of lncRNA XIST in CRC tissues and CRC cells was detected. CRC cells were transfected with pc-XIST, blank control si-XIST, or si-control, and then the effects of lncRNA XIST on CRC cell migration and invasion were investigated, along with the interaction between lncRNA XIST and miR-137. lncRNA XIST was upregulated in CRC tissues. Compared with HT29 cells that had low metastatic potential, XIST was markedly more highly expressed in LoVo cells that had a higher metastatic potential. Overexpression of XIST promoted the migratory and invasive potential of HT29 cells, while knockdown of XIST inhibited the migratory and invasive potential of LoVo cells. Moreover, epithelial–mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, and vimentin, exhibited corresponding expression changes. In addition, miR-137 was inhibited by XIST, and inhibition of miR-137 could reverse the effects of knockdown of XIST on the migratory and invasive potential of LoVo cells. Furthermore, enhancer of zeste homolog 2 (EZH2) was confirmed as a target of miR-137. Our data reveal that lncRNA XIST may promote tumor metastasis in CRC possibly through regulating the miR-137–EZH2 axis. lncRNA XIST may serve as a prognostic indicator for CRC progression.

LncRNA XIST regulates myocardial infarction by targeting miR-130a-3p.

The study was used to probe long noncoding RNA X-inactive specific transcript (lncRNA XIST)RNA expression profile and its influence on cell cycle, proliferation, and apoptosis in myocardial cells. We also aimed to explore the possible meditating relationship between XIST, PDE4D, and miR-130a-3p. Gene differential analysis was carried out using human lncRNA Microarray V3.0. quantitative real-time PCR was used to test mRNA expressions of XIST, miR-130a-3p, and PDE4D in normal cells and postmyocardial infarction (MI) cells. Western blot was applied to determine the protein expression profile of PED4D. Changes in viability and cell cycle/apoptosis of post-MI myocardial cells after silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry, respectively. The targeting relationship between miR-130a-3p and XIST, PDE4D in myocardial cells were verified by dual luciferase reporter assay. Simulated MI environment was constructed by performing anoxic preconditioning in normal cells to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were overexpressed in post-MI myocardial cells, whereas miR-130a-3p was underexpressed in post-MI myocardial cells. High-expressed XIST and PDE4D both promoted myocardial cell apoptosis. High-expressed XIST also inhibited myocardial cell proliferation. XIST-downregulated miR-130a-3p and PDE4D was a direct target of miR-130a-3p. LncRNA XIST promotes MI by targeting miR-130a-3p. MI induced by PDE4D can be reversed by miR-130a-3p.

Prognostic and clinicopathological roles of long non-coding RNA XIST in human cancers: a meta-analysis

Background: Mounting evidence has indicated that long non-coding RNA X-inactive specific transcript (XIST) could lead to cancer development and progression. This paper explored the association between XIST levels and clinical outcomes of cancer patients through a meta-analysis. Methods: We performed a systematic search through several databases, such as PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and WanFang, in order to collect cohort studies that reported XIST expression in various cancers. Two investigators independently screened documents, extracted data and evaluated the risk of bias of the included studies. Results: Eventually, data from 841 patients were selected from 12 studies. Our results suggested that there was a significant correlation between high level of XIST and poor overall survival (HR =1.791, 95% CI: 1.030–3.114, P<0.001) or short recurrence-free survival (HR =2.188, 95% CI: 1.453–3.297, P<0.469) in cancers. Furthermore, the results indicated that high XIST expression tends to be closely related with larger tumor size (OR =1.456, 95% CI: 1.186–1.786; P<0.258), positive lymph node metastasis (OR =1.381, 95% CI: 1.148–1.662; P<0.252), and advanced TNM stage (OR =1.496, 95% CI: 1.285–1.741; P<0.088). Conclusions: High expression of XIST in cancer tissue is valuable as a predictor in the prognosis of cancers.

Down-regulation of the long non-coding RNA XIST ameliorates podocyte apoptosis in membranous nephropathy via the miR-217-TLR4 pathway.

What is the central question of this study? What is the role of the long non-coding RNA X-inactive specific transcript (XIST), which is up-regulated in injured podocytes and membranous nephropathy, in the pathogenesis of membranous nephropathy? What is the main finding and its importance? XIST was up-regulated in kidney tissue with membranous nephropathy and in injured podocytes. Down-regulation of XIST inhibited podocyte apoptosis. XIST negatively regulated miR-217, and miR-217 modulated Toll-like receptor 4. Inhibition of XIST suppressed podocyte apoptosis induced by angiotensin II via miR-217. Membranous nephropathy is often characterized by glomerular podocyte injury. Up-regulation of the long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) has been verified in membranous nephropathy and in injured podocytes. Here the role of XIST in podocyte injury and membranous nephropathy was explored. Quantitative real-time PCR and western blot were performed to detect the expression of XIST and miR-217, and Toll-like receptor 4 (TLR4) protein, respectively. Podocyte apoptosis was evaluated with flow cytometry. Interaction between XIST and miR-217 was analysed by RNA immunoprecipitation and RNA pull-down assay. A dual luciferase reporter assay was used to examine the interplay between miR-217 and TLR4. Up-regulation of the lncRNA XIST and angiotensin II (Ang II) and kidney and podocyte injury were indicated in kidney tissue of patients with membranous nephropathy. Increase of XIST and apoptosis were induced by Ang II in podocytes. Down-regulation of XIST reversed podocyte apoptosis induced by Ang II. MiR-217 was negatively regulated by XIST. MiR-217 controlled TLR4 by targeting its 3'-untranslated region. XIST modulated TLR4 through miR-217 and inhibition of XIST reduced podocyte apoptosis induced by Ang II via regulating miR-217. Down-regulation of XIST ameliorates podocyte apoptosis via the miR-217-TLR4 pathway, which may improve membranous nephropathy.

Long non-coding RNA XIST promotes osteoporosis through inhibiting bone marrow mesenchymal stem cell differentiation.

The purpose of the present study was to identify the key long non-coding (lnc)RNAs in the occurrence and development of osteoporosis (OP) and to explore the associated molecular mechanism. First, the Gene Expression Omnibus (GEO) datasets, with key words ‘osteoporosis’ and ‘HG-133A’, were screened. RankProd R package was used to calculate the dysregulated lncRNAs in OP. Following this, bone marrow mesenchymal stem cells (BM-MSCs) harvested from 3-week-old Sprague Dawley rats were employed for detection of osteoblast differentiation. Following overexpression or interference with X-inactive specific transcript (XIST), osteogenesis-associated genes and proteins in BM-MSCs were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Alkaline phosphatase (ALP) and Alizarin Red S staining were also performed to measure the osteogenic ability of BM-MSCs. Results from the two datasets indicated that 6 lncRNAs were dysregulated in OP. Notably, XIST is key lncRNA in diverse diseases, and was subsequently selected for analysis. It was revealed that XIST was significantly upregulated in plasma and monocytes from patients with OP compared with the normal controls. Furthermore, results indicated that overexpression of XIST significantly inhibited osteoblast differentiation in BM-MSCs, as evidenced by the decreased expression of ALP, bone γ-carboxyglutamic acid-containing protein and runt related transcription factor 2, reduced ALP activity and a decreased number of calcium deposits. However, interference of XIST exhibited the opposite biological effects in BM-MSCs. Taken together, XIST was highly expressed in the serum and monocytes of patients with OP. In addition, the findings suggested that XIST could inhibit osteogenic differentiation of BM-MSCs.

Long non-coding RNA XIST promotes the development of esophageal cancer by sponging miR-494 to regulate CDK6 expression

ObjectiveEsophageal cancer is one of the deadliest cancers worldwide occurring at upper gastrointestinal tract. This study aimed to explore the possible role of long non-coding RNA X Inactive Specific Transcript (XIST) in the development of esophageal cancer. Material and methodsThe lncRNA XIST expressions both in esophageal cancer tissues and in cells were investigated. The TE-1 and SKGT-4 cells were transfected with LV-sh-XIST and LV-scramble for the further detection of the effects of XIST expression on cell biological processes, including proliferation, apoptosis and the expression of apoptosis-related proteins, migration, invasion and the expression of epithelial-mesenchymal transition markers. Additionally, the regulatory relationships between lncRNA XIST and miR-494, between miR-494 and CDK6, between miR-494/CDK6 and JAK2/STAT3 pathway were investigated. ResultsLncRNA XIST was overespressed in esophageal cancer tissues and cells. Suppression of XIST significantly inhibited the proliferation, migration and invasion, but induced apoptosis of two kinds of cells, TE-1 and SKGT-4. Moreover, miR-494 was down-regulated in esophageal cancer tissues and cells. XIST could sponge miR-494 and inhibition of miR-494 reversed the effects of XIST suppression on the malignant behaviors of TE-1 cells. Also, CDK6 was a target of miR-494 and CDK6 knockdown reversed the effects of miR-494 inhibition on the malignant behaviors of TE-1 cells. Besides, the expression of p-JAK2 and p-STAT3 was increased after miR-494 inhibition, which was reversed after inhibition of miR-494 and CDK6 at the same time. ConclusionsThe data presented in this study revealed that XIST abnormal expression may play an oncogenic role in the development of esophageal cancer via miR-494/CDK6 axis through JAK2/STAT3 signal pathway. This study may provide theoretical basis for the molecular mechanism investigation of esophageal cancer.