The role of exosomal LINC00853 in gastric cancer progression.

Abstract

378 Background: Examination of various substances contained in exosomes (EXOs) as biomarkers is being actively conducted. Long non-coding RNAs (lncRNAs) are garnering interest in the diagnosis of gastric cancer. In this experiment, we attempted to obtain lncRNAs that drive the onset and recurrence of gastric cancer and elucidate the mechanism to observe their potential as exosomal biomarkers. Methods: LncRNA expression profiling was conducted using ArrayStar Human LncRNA array 2.0 for the patient’s tissues who underwent endoscopic resection that reflected early gastric cancer onset and recurrence. The proliferation, apoptosis, invasion, and migration of AGS and MKN74 cells were measured after treatment with pcDNA over expressing vector and two different siRNAs. To observe the interaction between lncRNA and MAP17, RNA immunoprecipitation (IP) and electrophoretic mobility shift assay were conducted. EXOs were extracted from patient samples and gastric cancer cell lines, which were then administered to gastric cancer cells. Results: Five target lncRNAs (LINC00853, LINC00634, LINC01535, GAPLINC, and AC017002.1) were selected by performing a lncRNA microarray analysis. The validation results showed that LINC00853 was upregulated in gastric cancer tissues compared to that in paired adjacent non-cancer tissues. LINC00853 induced proliferation and suppressed apoptotic signaling of AGS and MKN74 cells. LINC00853 promoted the invasion and migration of AGS and MKN74 cells. LINC00853 bound with its neighbor gene MAP-17 and activated it via the downstream PDZK1/AKT signaling pathway. LINC00853 and MAP-17 cooperatively acted as oncogenes in gastric cancer. EXOs derived from patients with gastric cancer and those from gastric cancer cell lines (AGS, MKN74) contained LINC00853. Knock-down of LINC00853 decreased LINC00853 expression in EXOs, which, in turn, reduced the oncogenicity of LINC00853 exosome in AGS cells. Cellular and exosomal LINC00853 exert an oncogenic effect via MAP-17-related cell signaling in gastric cancer. Conclusions: Exosomal LINC00853 can be a candidate biomarker of occurrence of recurrence of gastric cancer.