CPNE8 Promotes Gastric Cancer Metastasis by Modulating Focal Adhesion Pathway and Tumor Microenvironment.

Little is known about the oncogenic role or biological function of copine Ⅷ (CPNE8) in gastric cancer (GC). Based on TCGA database, we screened for CPNE8 and analyzed the expression of CPNE8 in GC. The correlations between CPNE8 and clinical features were analyzed using TCGA and GEO databases. The prognostic value of CPNE8 was assessed using Cox analysis and Kaplan-Meier curves. The results showed that increased expression of CPNE8 was positively correlated with metastasis and can be considered an independent prognostic risk factor for poor survival. We found that CPNE8 can promote cell proliferation, migration, and invasiveness in GC using in vitro and in vivo experiments. Our study demonstrated that CPNE8 promotes tumor progression via regulation of focal adhesion, and these effects can be rescued by focal adhesion kinase (FAK) inhibitor GSK2256098 or knockdown of FAK. In addition, CPNE8 was correlated significantly with the infiltration of cancer-associated fibroblasts and immune cells, as demonstrated by various algorithms, and high CPNE8 expression predicted poor efficacy of immune checkpoint therapy. Our findings suggest that CPNE8 modulates focal adhesion and tumor microenvironment to promote GC progression and invasiveness and could serve as a novel prognostic biomarker in GC.

Overexpression of long non-coding RNA RP11-396F22.1 correlates poor prognosis of patients with early-stage cervical cancer.

OBJECTIVE: The expression level and clinical significances of long non-coding RNAs (LncRNAs) are presently unknown in the early-stage cervical cancer (CC). This study was aimed to explore the expression signatures of lncRNAs between normal and cervix carcinoma tissues and the prognostic value of LncRNAs in early-stage CC patients. MATERIALS AND METHODS: The patients diagnosed with FIGO stage I-IIb CC of the First Affiliated Hospital of Sun Yat-sen University between January 1st 2006 and December 31st 2009 were retrospectively reviewed. Molecular microarray was conducted to identify differentially expression profiles of LncRNAs. In situ hybridization was applied for detection of candidate lncRNAs in cervical tissues. RESULTS: A total of 2574 upregulated lncRNAs and 3270 downregulated lncRNAs with significantly differential expression (≥2.0-fold) were identified. Among the differentially expressed lncRNAs, RP11-396F22.1 expression was one of the most significantly overexpressed in the CC tissues compared to nomal cervical tissues (P<0.001). In situ hybridization confirmed RP11-396F22.1 expression was highly expressed in cancerous tissues. The results of Scratch and Transwell test showed that the migration ability decreased remarkably in transfected group (P<0.001). Moreover, the coding gene cpne8 was significantly upregulated by RP11-396F22.1 knockdown (P=0.035). CONCLUSIONS: These findings demonstrate that LncRNA RP11-396F22.1 might be a potent biomarker for CC progression.