Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown. LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments. LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial–mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/β-catenin pathway in an APC-dependent manner. Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.

Background: Long non-coding RNAs (lncRNAs) have been reported to be prognostic biomarkers in many types of cancer. We aimed to identify a lncRNA signature that can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC). Methods: Using a custom microarray, we retrospectively analyzed lncRNA expression profiles in 141 samples of ESCC and 81 paired non-cancer specimens from Sun Yat-Sen University Cancer Center (Guangzhou, China), which were used as a training cohort to identify a signature associated with clinical outcomes. Then we conducted quantitative RT-PCR in another 103 samples of ESCC from the same cancer center as an independent cohort to verify the signature. Results: Microarray analysis showed that there were 338 lncRNAs significantly differentially expressed between ESCC and non-cancer esophagus tissues in the training cohort. From these differentially expressed lncRNAs, we found 16 lncRNAs associated with overall survival (OS) of ESCC patients using Cox regression analysis. Then a 7-lncRNA signature for predicting survival was identified from the 16 lncRNAs, which classified ESCC patients into high-risk and low-risk groups. Patients with high-risk have shorter OS (HR: 3.555, 95% CI 2.195–5.757, p < 0.001) and disease-free survival (DFS) (HR: 2.537, 95% CI 1.646–3.909, p < 0.001) when compared with patients with low-risk in the training cohort. In the independent cohort, the 7 lncRNAs were detected by qRT-PCR and used to compute risk score for the patients. The result indicates that patients with high risk also have significantly worse OS (HR = 2.662, 95% CI 1.588–4.464, p < 0.001) and DFS (HR 2.389, 95% CI 1.447–3.946, p < 0.001). The univariate and multivariate Cox regression analyses indicate that the signature is an independent factor for predicting survival of patients with ESCC. Combination of the signature and TNM staging was more powerful in predicting OS than TNM staging alone in both the training (AUC: 0.772 vs 0.681, p = 0.002) and independent cohorts (AUC: 0.772 vs 0.660, p = 0.003). Conclusions: The 7-lncRNA signature is a potential prognostic biomarker in patients with ESCC and may help in treatment decision when combined with the TNM staging system.

Background Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it’s equivocal about the mechanism under HIPEC. Methods MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored. Results MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression. Conclusion MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.

Background: Chemoresistance is one of the causes of death in patients with gastric cancer (GC). Extensive studies have demonstrated that lncRNAs have important implications in GC chemoresistance, but their underlying mechanisms in driving GC chemoresistance remain poorly understood. Here, we investigated the function and molecular mechanism of lncRNA FAM66C in GC progression and chemoresistance. Methods: After long-term exposure to cisplatin (DDP) or paclitaxel (PTX), we successfully established two chemoresistance GC cell lines, HGC-27/DDP and HGC-27/PTX. The expression and biological function of FAM66C in GC cells were assessed using RT-PCR, drug sensitivity (IC50), cell viability (CCK8), apoptosis assay and in vivo xenograft models. The underlying mechanism of this lncRNA in GC chemoresistance was determined by Western blotting, RNA-FISH assay, RNA immunoprecipitation assay and rescue experiments. Results: FAM66C overexpression was observed in GC tissues and its elevated expression positively correlated with chemotherapy resistance and poor patient prognosis. Functional studies confirmed that it promoted GC proliferation and chemoresistance in vitro and in vivo . FAM66C induced nuclear YAP phosphorylation by interacting with nuclear YAP in a Hippo pathway-independent manner. Conclusion: In this study, we demonstrated that FAM66C facilitated GC chemoresistance by promoting the phosphorylation of nuclear YAP independently of the Hippo pathway. This lncRNA might serve as a novel prognostic biomarker and a potential therapeutic target for overcoming GC chemoresistance.