LncRNA XIST promotes pancreatic cancer migration, invasion and EMT by sponging miR-429 to modulate ZEB1 expression.

Pancreatic cancer (PC) has become a worldwide malignancy accompanied by high metastasis and extremely poor prognosis. The critical roles of long non-coding RNAs (lncRNAs) in PC are generally summarized as molecular sponges of microRNAs (miRNAs). We intended to investigate the biological function and mechanism of lncRNA X-inactive specific transcript (XIST) in PC progression, especially in PC cell migration and invasion. qPCR was applied to detect the expression levels of XIST and miR-429 in PC tissues and cell lines. The roles of XIST and miR-429 on PC cell migration, invasion and epithelial-mesenchymal transition (EMT) were assessed by wound healing, transwell, qPCR and Western blot assays, respectively. The regulating relationship among XIST, miR-429 and zinc finger E-box binding homeobox 1 (ZEB1) was investigated in PC cells. XIST was frequently upregulated while miR-429 was commonly downregulated in PC tissues, especially in metastatic PC tissues. Knockdown of XIST in two PC cell lines caused inhibition of migration, invasion and EMT capacities. Forced expression of miR-429 exerted the similar tumor suppressing effects. XIST repressed miR-429 expression thus upregulated ZEB1, one of the targets of miR-429. ZEB1 mediated the tumor suppressing roles of XIST knockdown in PC cells. We identified the critical axis of XIST/miR-429/ZEB1 in PC cell migration, invasion and EMT, which may aid in developing new therapeutic strategies for PC.

Shen J ，Hong L ，Yu D ，Cao T ，Zhou Z ，He S ... -  《-》

LncRNA ADPGK-AS1 promotes pancreatic cancer progression through activating ZEB1-mediated epithelial-mesenchymal transition.

Song S ，Yu W ，Lin S ，Zhang M ，Wang T ，Guo S ，Wang H ... -  《-》

LncRNA XIST promotes the epithelial to mesenchymal transition of retinoblastoma via sponging miR-101.

Accumulating evidence demonstrated that abnormal expression of long non-coding RNAs (lncRNAs) was closely associated with cancer development including retinoblastoma (RB). LncRNA X inactive specific transcript (XIST) has been found to function as an oncogene or a tumor suppressor in several cancers. However, the role and underlying mechanism of XIST in RB have not been clarified. The expression of XIST, microRNA (miR)- 101, zinc finger E-box binding homeobox (ZEB) 1, and ZEB2 was detected in human RB tissues and cell lines. The effects of XIST on the proliferation, migration, invasion, epithelial to mesenchymal transition (EMT), and apoptosis of RB cells were evaluated after downregulation of XIST. Furthermore, the mechanism of XIST was mainly focused on miR-101/ZEB1 or ZEB2 signaling. We found the expression of XIST, ZEB1 and ZEB2 was increased, whereas miR-101 was reduced in RB tissues and cells. Knockdown of XIST significantly suppressed the proliferation, migration, invasion and EMT, but promoted the apoptosis and caspase-3 activity. Moreover, we found that XIST functioned as a competing endogenous RNA (ceRNA) for miR-101 to regulate the de-repression of its endogenous targets ZEB1 and ZEB2. In conclusion, these findings suggest that XIST may facilitate the progression of RB through acting as a ceRNA for miR-101 to mediate the expression of ZEB1 and ZEB2. This may provide novel therapeutic options for RB.

Cheng Y ，Chang Q ，Zheng B ，Xu J ，Li H ，Wang R ... -  《-》

Long Non-coding RNA X-Inactive Specific Transcript Promotes Esophageal Squamous Cell Carcinoma Progression via the MicroRNA 34a/Zinc Finger E-box-Binding Homeobox 1 Pathway.

The long non-coding RNA X-inactive specific transcript (XIST) plays a crucial role in transcriptional silencing of the X chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-mesenchymal transition (EMT) regulation. This study aimed to investigate the impact of XIST on esophageal squamous cell carcinoma (ESCC) progression and its underlying mechanism involving the miR-34a/ZEB1/E-cadherin/EMT pathway. XIST and ZEB1 expression were analyzed using quantitative PCR and immunohistochemistry. XIST knockdown was achieved in KYSE150 ESCC cells using siRNA or shRNA lentivirus transfection. Proliferation, migration, and invasion abilities were assessed, and luciferase reporter assays were performed to confirm XIST-miR-34a-ZEB1 interactions. In vivo ESCC growth was evaluated using a xenograft mouse model. XIST and ZEB1 were upregulated in tumor tissues, correlating with metastasis and reduced survival. XIST knockdown inhibited proliferation, migration, and invasion of KYSE150 cells. It decreased ZEB1 expression, increased E-cadherin and miR-34a levels. Luciferase reporter assays confirmed miR-34a binding to XIST and ZEB1. XIST knockdown suppressed xenograft tumor growth. XIST promotes ESCC progression via the miR-34a/ZEB1/E-cadherin/EMT pathway. Targeting the XIST/miR-34a/ZEB1 axis holds therapeutic potential and serves as a prognostic biomarker in ESCC.

Guo B ，He M ，Ma M ，Tian Z ，Jin J ，Tian G ... -  《-》

Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p.

Lu W ，Zhang H ，Niu Y ，Wu Y ，Sun W ，Li H ，Kong J ，Ding K ，Shen HM ，Wu H ，Xia D ，Wu Y ... -  《Molecular Cancer》