LINC01268 promotes epithelial-mesenchymal transition,invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS

BACKGROUND Long non-coding RNAs(lncRNAs)with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer(GC),but their specific mechanisms and roles still need to be further elucidated.AIM To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression.METHODS Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues,cell lines and plasma.The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients.An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC.Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells.The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate(MARCKS),the PI3K/Akt signaling pathway,and the epithelial-mesenchymal transition(EMT)process in GC was demonstrated by western blot analysis.RESULTS The expression of LINC01268 was increased in GC tissues and cell lines.The expression level of LINC01268 was significantly correlated with lymph node metastasis,TNM stage,and tumor differentiation in patients with GC.Over-expression of LINC01268 indicated a poor prognosis for patients with GC,and it had a certain auxiliary diagnostic value for GC.In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC.CONCLUSION This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS,and ultimately promotes the invasion and metastasis of GC.LINC01268 may be a potential effective target for the treatment of GC.

Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway

BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.