Abstract 1158
Background
There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in tumor biology and development. The chromosome 8q24.21 locus is one of the most frequently amplified genomic regions in colon cancer, and many cancer-associated lncRNAs have been found in this 8q24 region. In this study, CASC21, located at 8q24.21, was selected to further experiments in colon cancer.
Methods
First, we downloaded RNA-sequencing data from the Cancer Genome Atlas (TCGA) database and analyzed the lncRNA expression profile in colon cancer. Then, CASC21, a lncRNA located at 8q24.21,was selected for further experiments. We performed qRT-PCR to detect the expression of CASC21 in colon cancer tissues and cell lines. Fluorescence in situ hybridization (FISH) assay was used to analyze the location of CASC21 in cells. Loss of function assays were used to test the efficacy of CASC21 on proliferation and invasion in colon cancer. Animal experiments including tumorigenicity studies and in vivo metastasis assays were used to determine the roles of CASC21 in tumor growth and metastasis in vivo.
Results
We found that CASC21 was significantly upregulated in colon cancer tissues compared with corresponding normal tissues. Up-regulation of CASC21 was associated with the tumor -node -metastasis (TNM) stage in colon cancer. Similarly, CASC21 was upregulated in colon cancer cell lines compared with colon epithelial cell line. FISH testing showed that CASC21 mainly located in the cytoplasm rather than the nucleus. Loss of function assays revealed that CASC21 knockdown significantly inhibited cell growth by inducing cell apoptosis and cell cycle arrest. Additionally, CASC21 knockdown promoted cell metastasis by facilitating epithelial mesenchymal transformation (EMT). Moreover, CASC21 expression was significant positively associated with MYC expression in both TCGA data and our cohort. Western blot assays showed that knockdown of CASC21 markedly reduced the expression levels of WNT targets including c-myc, β-catenin and cyclinD1. Animal studies also demonstrated that CASC21 promoted tumor growth and metastasis in colon cancer.
Conclusions
Our results provide the first evidence that CASC21 is a novel oncogenic regulator and a potential therapeutic target in colon cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Xiaoping Qian.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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