Non-coding RNA X-inactive Specific Transcript Research Articles

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.

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.

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.

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.

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

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 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.

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.

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.

Long non-coding RNA XIST exerts oncogenic functions in pancreatic cancer via miR-34a-5p.

Long non-coding RNAs (lncRNAs) have been implicated in the occurrence and progression of multiple cancers. In the present study, we investigated the role of lncRNA X inactive-specific transcript (XIST) in the development and progression of pancreatic cancer (PC). Firstly, we found that lncRNA XIST was markedly upregulated in PC tissues and PC cell lines, respectively. Overexpression of XIST significantly promoted the proliferation, migration and invasion, and suppressed cell apoptosis of BxPC-3 cells; knockdown of XIST significantly inhibited the proliferation, migration and invasion, and accelerated cell apoptosis of PANC-1 cells. Furthermore, BxPC-3 and PANC-1 cells transfected with different vectors were injected subcutaneously into nude mice to explore tumor formation. We found that XIST promoted tumor formation in vivo. Subsequently, we found that microRNA-34a-5p (miR-34a-5p) was downregulated in PC tissues, and predicted a poor prognosis in PC patients. In addition, the results indicated that miR-34a-5p is a target gene of XIST and was significantly negatively correlated with XIST. More importantly, we found that miR-34a-5p rescued the facilitation of malignant behavior mediated by XIST. These results indicated that XIST and miR-34a-5p may be potential effective therapeutic targets for PC.

Knockdown of long non-coding RNA XIST inhibits cell viability and invasion by regulating miR-137/PXN axis in non-small cell lung cancer

Long non-coding RNAs (lncRNAs) may serve as miRNA sponges to modulate the expressions of miRNA target genes. LncRNA X-inactive specific transcript (XIST) has been demonstrated to be upregulated and act as an oncogene in non-small cell lung cancer (NSCLC). However, the sponge role of XIST in NSCLC progression remains largely unknown. In this study, we demonstrated that XIST was substantially upregulated and miR-137 was aberrantly downregulated in NSCLC tissues and cells. XIST was identified to function as a competitive endogenous RNA (ceRNA) for miR-137 to promote NSCLC cell viability and invasion. Additionally, our results suggested that miR-137 targeted the 3’UTR of paxillin (PXN) to suppress NSCLC cell viability and invasion. Meanwhile, miR-137 was negatively correlated with PXN expression while XIST was positively correlated with PXN expression. More importantly, XIST positively regulated PXN levels by sponging miR-137 in vitro and in vivo. Collectively, our study provided the evidence for the cross-talk between XIST, miR-137, and PXN, shedding light on the therapy for NSCLC.

Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p

ObjectiveThe present study is to evaluate the biological functions of long non-coding RNA (lncRNA), X-inactive specific transcript, X-inactive specific transcript (XIST) in human epithelial ovarian cancer (EOC).MethodsXIST was upregulated in EOC cell lines, CAOV3 and OVCAR3 cells by lentiviral transduction. The effects of XIST overexpression on cancer cell proliferation, invasion, chemosensitivity and in vivo tumor growth were investigated, respectively. Possible sponging interaction between XIST and human microRNA hsa-miR-214-3p was further evaluated. Furthermore, hsa-miR-214-3p was overexpressed in XIST-upregulated CAOV3 and OVCAR3 cells to evaluate its effect on XIST-mediated EOC regulation.ResultsLentivirus-mediated XIST upregulation had significant anticancer effects in CAOV3 and OVCAR3 cells by suppressing cancer cell proliferation, invasion, increasing cisplatin chemosensitivity and inhibiting in vivo tumor growth. Hsa-miR-214-3p was confirmed to directly bind XIST, and inversely downregulated in XIST-upregulated EOC cells. In EOC cells with XIST upregulation, secondary lentiviral transduction successfully upregulated hsa-miR-214-3p expression. Subsequently, hsa-miR-214-3p upregulation functionally reversed the anticancer effects of XIST-upregulation in EOC.ConclusionUpregulation of lncRNA XIST may suppress EOC development, possibly through sponging effect to induce hsa-miR-214-3p downregulation.

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application for cancer therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug resistance of various tumors. Our study aimed to explore the role and molecular mechanisms of lncRNA X-inactive specific transcript (XIST) in chemoresistance of CRC to DOX. The expressions of XIST, miR-124, serum and glucocorticoid-inducible kinase 1 (SGK1) mRNA in DOX-resistant CRC tissues and cells were detected by qRT-PCR or western blot analysis. DOX sensitivity was assessed by detecting IC50 value of DOX, the protein levels of P-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) and apoptosis. The interactions between XIST, miR-124 and SGK1 were confirmed by luciferase reporter assay, qRT-PCR and western blot. Xenograft tumor assay was used to verify the role of XIST in DOX resistance in CRC in vivo. XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-π levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST-knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells. Moreover, SGK1-depletion-elicited decrease of DOX resistance was greatly restored by XIST overexpression or miR-124 inhibition in DOX-resistant CRC cells. Furthermore, XIST knockdown enhanced the anti-tumor effect of DOX in CRC in vivo. XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients.

Retracted Article: Long non-coding RNA XIST promotes proliferation, autophagy and inhibits apoptosis by regulating microRNA-30c/ATG5 axis in gastric cancer.

Background: Gastric cancer (GC) is a great threat to human health and life. Long non-coding RNA X inactive-specific transcript (XIST) and microRNA-30c (miR-30c) function as crucial players in the tumorigenesis of GC. Bioinformatics analysis suggests that miR-30c has a chance to interact with XIST and autophagy related 5 (ATG5). Moreover, ATG5 has been identified as a target of miR-30c in human intestinal epithelial cells. Hence, whether XIST could regulate cell proliferation, apoptosis and autophagy by miR-30c/ATG5 axis was further investigated in GC. Methods: The levels of XIST, miR-30c and ATG5 mRNA were measured by RT-qPCR assay. ATG5, p62, LC3-I, and LC3-II protein expression was detected by western blot assay. The relationships of XIST, miR-30c and ATG5 were examined by luciferase, RNA immunoprecipitation (RIP) and RNA pull down assays. Cell proliferation was assessed by MTS assay. Cell apoptotic rate was determined using flow cytometry. ATG5 protein expression in tissues was measured by immunohistochemistry (IHC) assay. Results: XIST was highly expressed in GC tissues and cell lines. XIST knockdown suppressed proliferation, autophagy and promoted apoptosis in GC cells. XIST inhibited miR-30c expression by direct interaction in GC cells. Furthermore, miR-30c depletion abrogated XIST deficiency-mediated anti-proliferation, pro-apoptosis and anti-autophagy effects in GC cells. Additionally, ATG5 was a target of miR-30c and XIST promoted ATG5 expression by sequestering miR-30c from ATG5 in GC cells. Conclusion: XIST knockdown suppressed proliferation, autophagy and induced apoptosis through regulating miR-30c/ATG5 axis in GC cells, hinting at the potential value of XIST in the management of GC.

The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth.

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the development and progression of many tumors. In this study, XIST was specifically upregulated in pancreatic carcinoma tissues and cell lines; a higher XIST expression was correlated to poorer clinicopathologic features. After XIST knockdown, the proliferation of PC cell lines was suppressed and cell cycle stagnated in G1 phase; XIST knockdown also reduced the protein levels of inhibitor of apoptosis-stimulating protein of p53 (iASPP) and Cyclin-dependent kinase 1 (CDK1), increased the protein level of P21, a potent CDK inhibitor. In PC cell lines, XIST and miR-140/miR-124, two tumor-associated miRNAs, could inversely regulate each other, respectively; miR-140/miR-124 could bind to XIST and the 3’UTR of PPP1R13L, respectively. XIST and miR-140/miR-124 exerted opposite effects on iASPP, CDK1, P21 and P27 proteins; whereas the effects of LV-sh-XIST on the indicated protein levels could be partially reversed by miR-140 and/or miR-124 inhibitor. In PC tissues, miR-140 and miR-124 expression was down-regulated, iASPP and CDK1 mRNA expression was up-regulated. XIST positively correlated with iASPP and CDK1, inversely correlated with miR-140 and miR-124, respectively. Taken together, our data indicated that XIST might be an oncogenic lncRNA that promoted proliferation of PC cell line through inhibiting miR-140/miR-124 expression and promoting cell cycle-related factor expression, and could be regarded as a therapeutic target in human pancreatic carcinoma.

LncRNA XIST Promotes Pancreatic Cancer Proliferation Through miR-133a/EGFR.

According to recent studies, long non-coding RNA X-inactive specific transcript (XIST) is involved in the development and progression of many malignant tumors including pancreatic cancer. We validated the detailed role of XIST in human pancreatic cancer (PC) cell lines and PC tissues so as to determine its exact function and the mechanism by which it affected PC proliferation. In our research, lncRNA-XIST was specifically upregulated in PC tissues and cell lines, and high XIST expression in PC was related to poorer prognosis (larger tumor size, perineural invasion, lymph node micrometastases, and shorter overall survival). XIST augmented PC cell proliferation. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes. In the present study, XIST and miR-133a reciprocally inhibited each other in PC cells. Exogenous miR-133a expression significantly inhibited PC cell proliferation. Moreover, as exhibited by luciferase reporter gene assays, miR-133a bound to XIST and the 3'UTR of EGFR by direct targeting. In PC tissues, miR-133a expression was down-regulated and EGFR expression was up-regulated; miR-133a was inversely correlated with EGFR and XIST, respectively; XIST was positively correlated with EGFR. Taken together, these findings will shed light on the role and mechanism of XIST/miR-133a/EGFR in regulating PC cells proliferation. XIST may serve as a potential therapeutic target in PC in the future. J. Cell. Biochem. 118: 3349-3358, 2017. © 2017 Wiley Periodicals, Inc.