Introduction: Growing evidence suggests that long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Nicotinamide nucleotide transhydrogenase antisense RNA 1 (lncRNA NNT-AS1) is up-regulated in some human tumors and functions as a tumor promoter. This study aimed to detect the effect of NNT-AS1 on cholangiocarcinoma (CCA) prognosis.
Materials and methods: In this study, we detected NNT-AS1 expression in CCA tissue samples and cell lines, and analyzed the association between NNT-AS1 expression levels and clinical parameters of CCA patients. Moreover, we conducted loss-of-function studies in CCA cancer cells to explore the biological function and molecular mechanism of NNT-AS1. NNT-AS1 was downregulated by using RNAi technology. Cell proliferation was examined by CCK8 and clone formation assays. Cell migration and invasion were determined by wound healing and transwell assays. Western blot assays were used to explore protein expression.
Results: In this study, NNT-AS1 was expressed at high levels in CCA and closely associated with poor prognosis of patients with CCA. NNT-AS1 knockdown impaired cell proliferation, suppressed CCA cell migration and invasion, and restrained tumor growth in vitro. Moreover, NNT-AS1 directly bounded to miR-485 and further regulated BCL9. Finally, rescue assays verified that NNT-AS1 modulated the tumorigenesis of CCA by regulating miR-485.
Conclusion: Taken together, NNT-AS1 played a critical biological role in the development of CCA. Our results elucidated NNT-AS1/miR-485/BCL9 axis might lead to a further understanding of the molecular mechanism of CCA.
Keywords: lncRNA, NNT-AS1, cholangiocarcinoma, BCL9