Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression

Chen, Dongliang; Ju, Huai-Qiang; Lu, Yong; Chen, Lezong; Zeng, Zhao-Lei; Zhang, Dongsheng; Luo, Hongyu; Wang, Feng; Qiu, Miaozhen; Wang, De-Shen; Xu, Dazhi; Zhou, Zhiwei; Pélicano, Hélène; Huang, Peng; Xie, Dan; Wang, Fenghua; Li, Yuhong; Xu, Rui‐hua

doi:10.1186/s13046-016-0420-1

Cited by 232 publications

(225 citation statements)

References 45 publications

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“…XIST inhibited cell proliferation and mobility in osteosarcoma by interacting with miR-21-5p and upregulating programmed cell death 4 (PDCD4) expression [30]. Knockdown of XIST exerted tumor-suppressive effects in gastric cancer by acting as a molecular sponge of miR-101 to modulate enhancer of zeste homolog 2 (EZH2) expression [31]. XIST overexpression enhanced cell growth in nasopharyngeal carcinoma through upregulating E2F3 in part through sponging miR-34a-5p [27].…”

Section: Discussionmentioning

confidence: 99%

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

Zhu

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: 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. Methods: 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. Results: 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. Conclusion: 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.

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Section: Discussionmentioning

confidence: 99%

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

Zhu

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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“…A recent study reported that the long non-coding RNA XIST functioned as a competing endogenous RNA to modulate EZH2 expression by mopping up miR-101 in gastric cancer [11], and that XIST is targeted and regulated by miR-92b in Hepatocellular carcinoma (HCC). In the present study, we investigated whether lncRNA-XIST functions as a ceRNA by interacting with miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury

Xie

Liu

et al. 2017

IJMS

107

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Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.

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“…LncRNA XIST has been reported to be up-regulated in many cancers [15, 36-38]. In cell lines created from the tissue of a patient with collecting duct carcinoma of the kidney, the XIST gene was found to have an increase in copy number [39].…”

Section: Discussionmentioning

confidence: 99%

“…XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression [15]. MiR-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by XIST [16].…”

Section: Introductionmentioning

confidence: 99%

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

Xiong

Wang

et al. 2017

Cell Physiol Biochem

100

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Backgrounds/Aims: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

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Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression

Cited by 232 publications

References 45 publications

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

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

Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

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