RESUMO
BACKGROUND: In recent years, gastric cancer (GC) has become a major cause of mortality among various malignancies worldwide with high incidence rates. Long non-coding RNA (lncRNAs) may serve as oncogenes and tumor suppressors in cancers. Therefore, we investigated the effect of LINC01314 on the development of GC cells in relation to the Wnt/ß-catenin signaling pathway. METHODS: Microarray data analysis was conducted to screen GC-related differentially expressed lncRNAs, followed by determination of the binding interaction between LINC01314 and kallikrein 4 (KLK4). Human GC cell line SGC-7901 was treated with over-expressed or silenced LINC01314 or KLK4 to investigate the mechanism LINC01314 affecting GC cellular activities. The levels of KLK4, Wnt-1, ß-catenin, cyclin D1, N-cadherin and E-cadherin were measured, and cell invasion and migration were evaluated. Next, the tumor weight, micro-vessel density (MVD) and the expression of VEGF-C and VEGFR-3 in transplanted tumors were measured. RESULTS: LINC01314 was poorly expressed in GC cells and KLK4 was revealed to be a direct target gene of LINC01314. Overexpressed LINC01314 or silencing of KLK4 led to inhibited GC cell migration and invasion, corresponding to decreased Wnt-1, ß-catenin, cyclin D1 and N-cadherin while increased E-cadherin. Also, in response to over-expression of LINC01314 or silencing of KLK4, tumor weight and the MVD of transplanted tumors were reduced and angiogenesis was suppressed, which was indicated by down-regulated positive expression of VEGF-C and VEGFR-3. CONCLUSION: The findings indicated that over-expression of LINC01314 down-regulated KLK4 to inhibit the activation of the Wnt/ß-catenin signaling pathway, thus suppressing migration, invasion, and angiogenesis in GC cells, which provides new insight for the treatment of GC.
RESUMO
Hepatoblastoma (HB), as a common pediatric liver malignancy, is composed of a variety of subgroups with different clinical outcomes. Long-noncoding RNA (lncRNA) has crucial roles in cancer biology. However, the association between lncRNA and HB has not been fully investigated. In this study, we screened lncRNA expression profiles that were annotated from the GSE75271 dataset. A total of 225 differentially expressed lncRNAs (DELs) were identified based on comparison between three prognostic subgroups, and seven of them (XR_241302, XR_923061, NR_038322, XR_951687, XR_934593, NR_120317 and XR_93406) that exhibited highly predictive accuracies were selected for functional analysis. Weighted gene correlation network analysis (WGCNA) was employed to predict the biological functions of the seven DELs. The Hippo-YAP signaling pathway was predicted to be the most statistically significant predicted pathway associated with the seven DELs. Furthermore, we performed in vitro experiments to validate the biological function of one DEL, NR_120317 (LINC01314). Our results showed decreased proliferation and migration activities of HB cells overexpressing LINC01314. Moreover, mechanistic investigations revealed that LINC01314 overexpression inhibited nuclear translocation of YAP, by inducing MST1 expression and promoting phosphorylation of LATS1 and YAP, consequently downregulating the expression of cell cycle regulatory proteins (MCM7 and cyclin D1). Taken together, our findings provide evidence for LINC01314 as a potential biomarker and anti-cancer therapeutic target in patients with HB.