Long Non-Coding RNA LINC01094 Promotes Metastasis of Gastric Cancer through Activating RhoA/Rho-Associated Coiled-Coil Kinase Pathway

Abstract

Purpose: The morbidity and mortality of gastric cancer (GC) remain high and are rising. Early diagnosis and treatment can lower mortality. However, early GC (EGC) is challenging to diagnose and often accompanied by lymphatic metastasis. Therefore, this study sought to find long non-coding RNAs (lncRNAs) that are diagnostic and associated with metastasis. Methods: Bioinformatics was employed to analyze the intersection of up-regulated lncRNAs in three Gene Expression Omnibus (GEO) datasets associated with GC. The long non-coding RNA LINC01094 (LINC01094) expression levels in GC tissues and adjacent tissues were determined by Quantitative real time polymerase chain reaction (qRT-PCR). GC patients was allocated to non-metastasis and metastasis groups, and their expression levels of LINC01094 were estimated. At the cellular level, LINC01094 expression levels in human GC cell lines (AGS and SNU-16) and human gastric epithelial cell line (GES-1) were also estimated with qRT-PCR. Subsequently, cell cloning, transwell and wound healing assays were used to determine the effect of knockdown or overexpression of LINC01094 on human gastric adenocarcinoma cell line (AGS) cell proliferation, migration and invasion. Western blot was used to measure the role of LINC01094 in epithelial-mesenchymal-transition (EMT)-related proteins and RhoA/Rho-associated coiled-coil kinase (ROCK) pathway. Results: Bioinformatics analysis revealed significantly high expression of LINC01094 in GC tissues. qRT-PCR results further confirmed that LINC01094 expression was significantly raised in GC tissues, GC metastasis group, and GC cell lines. Additionally, LINC01094 overexpression significantly encouraged AGS cells to proliferate, migrate and invade, lowered the E-cadherin expression and boosted the protein expressions of N-cadherin, Snail, RhoA and ROCK2. Knockdown of LINC01094, however, produced the opposite result to the LINC01094 overexpression. Conclusions: LINC01094 facilitates AGS cell proliferation, migration, invasion and EMT by activating RhoA/ROCK pathway. Therefore, LINC01094 has the potential to be an early diagnostic biomarker and therapeutic target for GC.