Abstract
BackgroundIn 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/β-catenin signaling pathway.MethodsMicroarray 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, β-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.ResultsLINC01314 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, β-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.ConclusionThe findings indicated that over-expression of LINC01314 down-regulated KLK4 to inhibit the activation of the Wnt/β-catenin signaling pathway, thus suppressing migration, invasion, and angiogenesis in GC cells, which provides new insight for the treatment of GC.
Highlights
In recent years, gastric cancer (GC) has become a major cause of mortality among various malignan‐ cies worldwide with high incidence rates
The results revealed that compared with the negative control (NC) group, the luciferase activity of wild type (Wt)-KLK4 was attenuated in the OE-LINC01314 group (p < 0.05) while that of Mut-KLK4 did not differ greatly (p > 0.05)
These results demonstrate that LINC01314 could bind to KLK4 gene
Summary
Gastric cancer (GC) has become a major cause of mortality among various malignan‐ cies worldwide with high incidence rates. Gastric cancer (GC) is one deadliest cancer all around the world, constituting for a quarter of all carcinoma occurrence rates across China [1]. It is the chief cause of cancer-related deaths, and estimations suggest that. 400,000 new diagnosis and 300,000 deaths occur every year, in China [2]. While the worldwide occurrence of GC has significantly reduced and the long-term survival rate has improved dramatically in the past decades, it remains to be a crucial contributor to the global cancer burden [4].
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