Long non-coding RNA ZFAS1 (zinc finger antisense 1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer.
Researchers from Shanghai Jiao Tong University School of Medicine analyzed paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients. Quantitative real-time PCR analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT.
ZFAS1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (p < 0.01), and its expression level was significantly correlated with TNM stage, vascular invasion and lymph node metastasis (p < 0.05). ZFAS1 and ZEB1 were also increased in patients’ plasma. Moreover, ZFAS1 promoted proliferation, invasion and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin.
LncRNA-ZFAS1 promotes the progression of colonic cancer cells in vitro
(A) Relative expression levels of ZFAS1 and ZEB1 in SW620 cells, after treatment with SiRNA-ZFAS1or Si-NC. (B) CCK-8 assay was performed to determine the cell viability of Si-NC/Si-ZFAS1 cells. (C) qRT-PCR analysis of ALPi expression level in ZFAS1-knocked down cells compared to the negative control-group cells. (D) A colony forming assay was performed to determine the proliferation of Si-NC or Si-RNA ZFAS1-transfected SW620 cells. The colonies were counted and photographed. (E) Transwell assays were performed to determine the migratory and invasive abilities of Si-NC/Si-ZFAS1-transfected SW620 cells. *P < 0.05; **P < 0.01.
LncRNAZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.