| Purpose: The dysregulation of long non-coding RNA(IncRNA)has increasingly been linked to human cancer.However,themolecular mechanism of most lncRNAs and their clinical values in gastric cancer(GC)tissue,gastric juice,serum,and cells remain largely unknown.The specific aim of the present study was to screen a new gastric-cancer-associated lncRNA SLC7A11-AS1,and explore its expression in the clinical pathological characteristics and proliferation of gastric cancer cells for human GC.Method: The preliminary screenings of lncRNAs and coding transcripts of mRNA in GC specimens and respective adjacent noncancerous tissues(ANT)were conducted by microarray.Reverse transcription quantitative polymerase chain reactions(RT-qPCR)were used for large-scale analysis of 100 pairs of human GC tissues and respective ANT and analysis peripheral blood mononuclear cells(PBMCs)to verify the involvement of SLC7A11-AS1 in tumorigenesis and development of GC,and analysis of SLC7A11-AS1 expression level in GC cell lines.The association between the level of SLC7A11-AS1 and the clinicopathological characteristics were further analyzed and the diagnostic values and prognosis was evaluated.Knock down expression of SLC7A11-AS1 in SLC7A11-AS1 high GC cell lines were applied to investigate its roles in GC tumorigenic proliferation regulation via SLC7A11 and ASK1-p38MAPK/JNK signaling pathway in vitro.Moreover,CCK-8 proliferation assay and flow cytometry were performed to study the effects of SLC7A11-AS1 on GC cell proliferation and cell cycle progression.Results:1.Total of 4,643 lncRNAs and 3,944 mRNAs with significantly differential expression change were identified more than two fold in GC tissues and respective ANT by microarray.In lncRNAs group,there were 2,617 up and 2,026 down expressed,respectively.In mRNAs group,there were 1,948 mRNAs upregulated and 1,996 downregulated,respectively.2.SLC7A11-AS1 level was significantly decreased in the majority of GC tissues and PBMCs,and the reduction of SLC7A11-AS1 correlated with the distal metastasis,macroscopic types,tumor stage,CEA and Ki-67.Decreased expression of SLC7A11-AS1 predicted poor prognosis as a independent risk factor for tumor proliferation in GC.3.SLC7A11-AS1 expression in GC tissues(0.632)and PBMCs(0.791)for detecting GC with the sensitivity was 87.00% and the specificity was 44.00% and the sensitivity was 90.48% and the specificity was 57.58%,respectively.4.SLC7A11 was up regulated in human GC tissues compared with ANT,and SLC7A11 also up-regulated in the SLC7A11-AS1 low cancer tissues compared with the SLC7A11-AS1 high cancer tissue.Cyclin D1 expression was significantly increased in cancer tissues compared with ANTs and Cyclin D1 level in the SLC7A11-AS1 low cancer tissues was higher than the SLC7A11-AS1 high cancer tissues.The expression of SLC7A11-AS1 was negatively correlated with the expression of SLC7A11.5.SLC7A11 upregulation was acquired based on adenoviral-based sh-SLC7A11-AS1 knockdown SLC7A11-AS1 in SGC-7901、MGC-803、HGC-27 cells.6.The cell significant G1/S progression was observed when functional knock-down SLC7A11-AS1 in SGC-7901,MGC-803 and HGC-27 cellscompared to negative control group.7.The expression level of Gclm,ASK1,c-jun,and Cyclin D1 was up-regulated significantly and p38 expression was down-regulated when SLC7A11-AS1 was knocked down,but p38 and ASK1 was no statistically significant difference in MGC-803 and HGC-27,respectively.Conclusions:1.SLC7A11-AS1 is a new biomarker for human GC and decreased SLC7A11-AS1 expression maybe usually indicates a poor prognosis.2.SLC7A11-AS1 as a tumor suppressor decreased SLC7A11 expression.3.SLC7A11-AS1 suppresses cell proliferation and cell cycle progression.4.SLC7A11-AS1 regulates cell proliferation by ASK1-p38MAPK/ JNKsignaling in GC. |
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