OBJECTIVE: Growing evidence has shown that long non-coding RNAs (lncRNAs) can serve as prospective markers for survival in patients with colorectal adenocarcinoma. In this study, we mainly focused on the potential roles of lncRNA- ZDHHC8P1 in the development process of colorectal cancer (CRC) via miR-34a. PATIENTS AND METHODS: Quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) was used to detect the expression of lncRNA ZDHHC8P1 in CRC patients and cell lines. The relationships between the expression level of ZDHHC8P1, patient clinicopathological parameters and overall survival (OS) were analyzed using the univariate Ka-plan-Meier method. Proliferation ability was tested by Cell Counting Kit-8 (CCK-8) and cyclin D1 assay, through loss- and gain-of-function approaches. Moreover, the cycle distribution and wound-healing assay were used to measure the function of progression and metastasis in CRC cell lines. Furthermore, Luciferase activity proved the relationship between miR-34a and ZDHHC8P1. RESULTS: We found that lncRNA-ZDHHC8P1 was highly expressed in heatmap of colon cancer with lncRNAtor. Additionally, the lncRNA ZDHHC8P1, an independent prognostic factor for overall survival, was increased in CRC and correlated positively with CRC progression. Most importantly, through loss- and gain-of-function approaches, we showed that ZDHH-C8P1 promotes progression and metastasis in vitro. What’s more, the ZDHHC8P1 expression level was reversely correlated with miR-34a expression in patients with CRC. Mechanistically, miR-34a was identified as an important ZDHHC8P1 functional target. CONCLUSIONS: According to the results, this work uncovers a previously unappreciated ZDH-HC8P1/miR-34a regulatory axis in controlling progression and metastasis of CRC and suggests that interfering with lncRNA-ZDHHC8P1 and miR-34a could be a viable approach to treat late-stage metastatic CRC patients. © 2019 Verduci Editore s.r.l. All Rights Reserved.