Long Non-Coding RNA Duxap8 Facilitates Cell Proliferation and Induces Apoptosis in Colorectal Cancer via miR-519b/ZNF277 Axis.

Abstract

IntroductionLong non-coding RNAs (LncRNAs) play a critical role in development and progression of various cancers. More and more researchers pay attention to the effect of lncRNA on regulating the cancer. However, the function and mechanism of Duxap8 in colorectal cancer have not been studied.MethodsReverse transcription quantitative PCR (RT-qPCR), cell counting kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation assay, flow cytometry, TdT-mediated dUTP nick-end labeling (TUNEL), Western blot, hematoxylin-eosin staining (HE), in situ hybridization (ISH) analysis, immunohistochemistry (IHC) and tumor transplantation experiment were performed to investigate the function and mechanism of Duxap8 in colorectal cancer.ResultsWe found that the expression level of Duxap8 in colorectal cancer was closely correlated with tumor size (P = 0.024), tumor depth (P = 0.035) and lymphatic invasion (P =0.067) among 50 colorectal cancer patients. Then, we proved that the expression level of Duxap8 was significantly increased in human colorectal cancer tissues and cell lines. Functionally, Duxap8 knockdown inhibited the proliferation and induced the apoptosis of colorectal cancer cells, while Duxap8 overexpression facilitated the proliferation and suppressed the apoptosis in colorectal cancer in vitro. Moreover, knockdown of Duxap8 inhibited the size and weight of tumors in mice injected with colorectal cancer cells, overexpression of Duxap8 promoted the growth of colorectal cancer cells in vivo. Mechanically, we found that Duxap8 was principally located in the cytoplasm. Furthermore, Duxap8 functioned as a competing endogenous RNA to induce the development and progression of colorectal cancer through sponging miR-519b-3p to upregulate ZNF277.DiscussionTaken together, our results demonstrated that Duxap8 enhanced the expression level of ZEB1 to promote via competing for miR-519b-3p, which might be a promising molecular therapeutic target of colorectal cancer.