Abstract
BackgroundLong non-coding RNAs (LncRNAs) are a class of newly identified transcripts recognized as critical governors of gene expression during human carcinogenesis, whereas their tumor-suppressive or tumor-promoting effects on gastric cancer (GC) are required for further investigation. In the study, we identify the expression pattern of a novel lncRNA LINC00242 in GC and its possible permissive role in the development of GC.MethodsThe study included 68 pairs of GC and adjacent normal gastric tissue samples. The viability, migration, and invasion of cultured human GC cells HGC27 were evaluated by CCK-8 and Transwell chamber assays. In vitro tube formation of human brain microvascular endothelial cells (HBMVECs) in HGC27 cell coculture was detected. The regulatory network of LINC00242/miR-141/FOXC1 was verified using dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Subcutaneous xenografts of HGC27 cells were performed in nude mice.ResultsLINC00242 was highly expressed in GC tissues and cells and contributed to poor prognosis. LINC00242 knockdown inhibited HGC27 cell viability, migration and invasion, and tube formation of HBMVECs. LINC00242 interacted with miR-141 and positively regulated FOXC1, a target gene of miR-141. LINC00242 knockdown was partially lost in HGC27 cells upon miR-141 inhibition or FOXC1 overexpression. The tumor-promoting effect of LINC00242 on GC was demonstrated in nude mice.ConclusionTaken together, the present study demonstrates the oncogenic role of the LINC00242/miR-141/FOXC1 axis in GC, highlighting a theoretical basis for GC treatment.
Highlights
Long non-coding RNAs (LncRNAs) are a class of newly identified transcripts recognized as critical governors of gene expression during human carcinogenesis, whereas their tumor-suppressive or tumor-promoting effects on gastric cancer (GC) are required for further investigation
LINC00242 was upregulated in GC tissues and cells We firstly obtained differential expression genes (DEGs) between GC tissues and normal tissues by analyzing raw data of GC-related expression datasets GSE79973, GSE19826 and GSE65801 that deposited in the Gene Expression Omnibus (GEO)
Subsequent results (Fig. 1d) displayed 255 overlapping genes with significant difference in the three datasets, among which, there was one lncRNA, LINC00242, which was highly expressed in GC in the three datasets
Summary
Long non-coding RNAs (LncRNAs) are a class of newly identified transcripts recognized as critical governors of gene expression during human carcinogenesis, whereas their tumor-suppressive or tumor-promoting effects on gastric cancer (GC) are required for further investigation. FOXC1, a member of the FOX family, is essential for cell proliferation, migration, invasion, as well as vascular formation and maturation [13, 14]. Their specific mechanism in angiogenesis of GC remains largely unknown. The role of the newly discovered lncRNA LINC00242 in the cell invasion, metastasis, and angiogenesis of GC and its possible mechanisms is explored, which may help to provide a novel direction for GC treatment
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