LncRNA CASC9 promotes tumorigenesis by affecting EMT and predicts poor prognosis in esophageal squamous cell cancer

The purpose of this study was to explore the clinical significance and biological function of long noncoding RNA CASC9 (CASC9) in esophageal squamous cell carcinoma (ESCC).

Quantitative Real-time PCR (qRT-PCR) was used to determine the expression of CASC9 in ESCC tissues and cell lines. Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of CASC9. The correlation between the CASC9 levels and the clinicopathological factors of the patients was also analyzed. Then, the survival was assessed by the Kaplan-Meier method and proportional hazards model. The effects of CASC9 on ESCC cells were evaluated by Cell Counting Kit-8 (CCK-8), migration and invasion. Finally, several EMT markers expression was detected by Western blot.

We found that CASC9 was significantly upregulated in ESCC cell lines and clinical tissues. The CASC9 levels discriminated ESCC tissues from normal tissues with an area under the ROC curve (AUC) of 0.813. In addition, there is statistical significance between CASC9 expression level and tumor stage, lymph nodes metastasis, and clinical stage. Kaplan-Meier analysis indicated that high CASC9 expression had a significant impact on overall survival (p = 0.014) and disease-free survival (p = 0.0025). Moreover, CASC9 expression was an independent prognostic marker of overall survival and disease-free survival in a multivariate analysis. In vitro assay indicated that inhibition of CASC9 could suppress proliferation, migration, and invasion in ESCC. Further mechanistic studies found that aberrant CASC9 expression could modulate the expression levels of markers of EMT.

Our data highlight the pivotal role of CASC9 as a novel diagnostic, prognostic biomarker and a potential therapeutic target of ESCC.