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

Abstract

Hailiang Liang,1,* Jin Wang,2,* Peng Zhang,1,* Wei Yang,3 Yang Yang,4 Yin Zhi,1 Wei Wu,3 Xiaoqiang Dong1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of General Surgery, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, 215006, People’s Republic of China; 3Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China; 4Department of Anesthesiology, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiang Dong; Wei Wu Email [email protected]; [email protected]: Long 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.Methods: Reverse 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.Results: We 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.Discussion: Taken 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.Keywords: Duxap8, miR-519b-3p, ZNF277, colorectal cancer

Keywords

• duxap8
• mir-519b-3p
• znf277
• colorectal cancer