Upregulation of long noncoding RNA zinc finger antisense 1 enhances epithelial–mesenchymal transition in vitro and predicts poor prognosis in glioma

Abstract

Increasing evidence indicates that long noncoding RNAs play important roles in development and progression of various cancers. Zinc finger antisense 1 is a novel long noncoding RNA whose clinical significance, biological function, and underlying mechanism are still undetermined in glioma. In this study, we reported that zinc finger antisense 1 expression was markedly upregulated in glioma and tightly correlated with clinical stage. Moreover, patients with high zinc finger antisense 1 expression had shorter survival. Multivariate Cox regression analysis provided a clue that, probably, zinc finger antisense 1 level could serve as an independent prognostic factor for glioma. Functionally, zinc finger antisense 1 acted as an oncogene in glioma because its knockdown could promote apoptosis and significantly inhibit cell proliferation, migration, and invasion. Furthermore, zinc finger antisense 1 silencing could result in cell cycle arrest at the G0/G1 phase and correspondingly decrease the percentage of S phase cells in both U87 and U251 cell lines. Moreover, it was found that silenced zinc finger antisense 1 could impair migration and invasion by inhibiting the epithelial-mesenchymal transition through reducing the expression of MMP2, MMP9, N-cadherin, Integrin β1, ZEB1, Twist, and Snail as well as increasing E-cadherin level in glioma. Taken together, our data identified that zinc finger antisense 1 might act as a valuable prognostic biomarker and potential therapeutic target for glioma.

DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells

“…Previous reports have shown that ZFAS1 is highly expressed in glioma tissues and cells, and ZFAS1 downregulation significantly inhibits glioma cells proliferation, migration, and invasion, and it accelerates apoptosis. 39,40 The expression of ZFAS1 is downregulated in breast cancer and acts as a tumor-suppressive gene; 41 in contrast, ZFAS1 is upregulated in colorectal, gastric, hepatocellular, bladder, and ovarian cancers, acting as an oncogene; and ZFAS1 is dysregulated in various malignant tumors and is involved in tumor proliferation, invasion, metastasis, apoptosis, cell cycle, and drug resistance. 42 Many proteins interact with the transcribed RNAs to form RNPs.…”

ZFAS1: a novel tumor-related long non-coding RNA

“…Then, knockdown of ZFAS1 in glioma cell lines significantly suppressed proliferation, migration and invasion. Lv et al [26] reported that ZFAS1 expression was markedly upregulated in glioma tissues and tightly correlated with clinical stage and shorter survival. Then they found knockdown of ZFAS1 in glioma cell lines could promote apoptosis, and inhibit cell proliferation, migration, and invasion.…”

“…It has been demonstrated that ZFAS1 could regulate the expression of above gene, thus promote the tumorgenesis and progression of various cancers such as melanoma, glioma, colorectal cancer and gastric cancer [26, 30, 37, 47]. However, whether these effect are direct or indirect, is unknown until now.…”

Prognostic and clinicopathological role of long non-coding RNA ZFAS1 in various carcinomas

“…However, there were opposite findings that elevated lncRNA ZFAS1 occurred in gastric cancer, hepatocellular carcinoma and glioma. The function of lncRNA ZFAS1 in cancer cells might be cell type-dependent [12][13][14][15][16][17][18][19][20]. Therefore, we need a systematical and comprehensive meta-analysis to explore whether overexpression of ZFAS1 in tumor are related to worse outcome.…”

“…According to the inclusion and exclusion criteria, 747 patients from 8 eligible studies were included in this meta-analysis [12][13][14][15][16][17][18][19]. The screening process was shown in Figure 1.…”