CERS6‐AS1 contributes to the malignant phenotypes of colorectal cancer cells by interacting with miR‐15b‐5p to regulate SPTBN2

Abstract

Abstract Accumulating evidence indicates that long noncoding RNAs (lncRNAs) act as tumor promoters or suppressors in various types of cancer. Previous investigations suggest that ceramide synthase 6 (CERS6) antisense RNA 1 (CERS6‐AS1) acts as an oncogene in breast cancer; however, its role in colorectal cancer is unknown. This study aimed to explore the molecular mechanism of CERS6‐AS1 in colorectal cancer. Gene expression in colorectal cancer was examined using reverse transcription‐quantitative polymerase chain reaction and western blot analyses. The viability and proliferation of colorectal cancer cells were measured by Cell Counting Kit‐8 assays and colony formation assays. The migratory and invasive capacities of the colorectal cancer cells were assessed by Transwell assay. Cell stemness was examined by sphere‐formation assay. Mechanistically, RNA pull‐down assays, RNA immunoprecipitation assays, and luciferase reporter assays were performed to explore the relationship among CERS6‐AS1, miR‐15b‐5p and spectrin beta, non‐erythrocytic 2 (SPTBN2). Moreover, a xenograft tumor model was established to investigate the role of CERS6‐AS1 in vivo. We found that CERS6‐AS1 and SPTBN2 were highly expressed in colorectal cancer tissues and cells. CERS6‐AS1 depletion inhibited cell viability, proliferation, migration, and invasion; the epithelial‐mesenchymal transition process and stemness. It suppressed xenograft tumor growth in colorectal cancer. Moreover, SPTBN2 levels were positively regulated by CERS6‐AS1 and negatively regulated by miR‐15b‐5p in colorectal cancer cells. Rescue assays revealed that SPTBN2 reversed the inhibitory effect of CERS6‐AS1 deficiency on the malignant behaviors of colorectal cancer cells. Overall, the lncRNA CERS6‐AS1 facilitates malignant phenotypes of colorectal cancer cells by targeting miR‐15b‐5p to upregulate SPTBN2.

Keywords

• CERS6‐AS1
• colorectal cancer
• malignant phenotypes
• miR‐15b‐5p
• SPTBN2