Expression Of lncRNA XIST Research Articles

Long non-coding RNA XIST promotes cell growth and invasion through regulating miR-497/MACC1 axis in gastric cancer.

Abnormal expression of long non-coding RNA (lncRNAs) often contributes to unrestricted growth and invasion of cancer cells. LncRNA XIST expression is up-regulated in several cancers, however, its modulatory mechanism in gastric cancer (GC) has not been elucidated. In the present study, we found that XIST expression was significantly increased in GC tissues and cell lines. LncRNA XIST promoted cell cycle progression from the G1 phase to the S phase and protected cells from apoptosis, which contributed to GC cell growth. LncRNA XIST also contributed to GC cell invasion both in vitro and in vivo. We revealed that XIST functioned as competing endogenous RNA to repress miR-497, which controlled its down-stream target MACC1. We proposed that XIST was responsible for GC cell proliferation and invasion and XIST exerted its function through the miR-497/MACC1 axis. Our findings suggested that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in GC patients.

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

BackgroundLong non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown.MethodsReal-time PCR analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients. The biological function of lncRNA XIST on gastric cancer cells were determined both in vitro and in vivo. The regulating relationship between lncRNA XIST and miR-101 was investigated in gastric cancer cells.ResultslncRNA XIST was significantly up-regulated in gastric cancer tissues and cell lines. Overexpression of lncRNA XIST was markedly associated with larger tumor size, lymph node invasion, distant metastasis and TNM stage in gastric cancer patients. Functionally, knockdown of lncRNA XIST exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted.ConclusionslncRNA XIST is up-regulated and is associated with aggressive tumor phenotypes and patient survival in gastric cancer, and the newly identified lncRNA XIST/miR-101/EZH2 axis could be a potential biomarkers or therapeutic targets for gastric cancer patients.

Abstract B22: Loss of LncRNA XIST induces Epithelial to Mesenchymal Transition in Breast Cancer

Abstract Brain is one of the major sites of metastasis of breast cancer, and approximately 20% of patients with aggressive breast cancer eventually develop the metastatic disease in the brain. Long non-coding RNAs (lncRNA) have recently drawn much attention due to their wide functional variations and potential roles in tumor progression. By performing lncRNA array analysis comparing non-metastatic primary tumors with brain metastatic tumors from breast cancer patients, we identified that lncRNA XIST expression was significantly down-regulated in brain metastatic tumors. The result of Taqman PCR validated the results in tumor samples and also indicated that XIST expression was down-regulated in brain metastatic cell lines compared to non-brain metastatic cell lines. Moreover, we found that the XIST expression was negatively correlated with breast cancer stage and brain metastasis-free survival. XIST is located on the q arm of the X chromosome (Xq13-2) and plays a critical role in the X inactivation, thus providing dosage equivalence between males and females. Importantly, XIST has been found to be down-regulated in several types of tumors including breast cancer. Loss of XIST facilitates escape of some X chromosome genes from inactivation. To further study the effect of XIST down-regulation on tumor cells, we knocked down XIST expression in MCF7 by siRNA. We found that the knockdown of XIST drastically altered the morphology of MCF7 cell from epithelial to mesenchymal type. Furthermore, several epithelial-mesenchymal transition (EMT)-related genes including ZEB2 and SNAIL were upregulated in the XIST knockdown cells. In addition, the results of qPCR, western blot and immunocytochemical analysis showed that the epithelial marker E-cad was significantly down-regulated, while mesenchymal markers N-cad and Vimentin were upregulated in MCF7-siXIST, SKBR-siXIST and ZR751-siXIST cells compared to the control cells. To further examine the effect of XIST knockdown in vivo, we transplanted MCF7-siXIST, SKBR3-siXIST and their control cells by intra-cardiac injection into nude mice. We found that knockdown of XIST significantly enhanced tumor metastasis, especially in the brain. Our results strongly suggest that lncRNA XIST plays a critical role in tumor progression and metastasis by inducing EMT. Citation Format: Yin Liu, Fei Xing, Kerui Wu, Sambad Sharma, Kounosuke Watabe. Loss of LncRNA XIST induces Epithelial to Mesenchymal Transition in Breast Cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B22.