LncRNA-MIR17HG mediated upregulation of miR-17 and miR-18a promotes colon cancer progression via activating Wnt/β-catenin signaling

Guangwen Yuan, Bin Liu, Wenqian Han, Daqi Zhao


Background: Long non-coding RNA MIR17HG (miR-17-92 cluster host gene lncRNA) is synthesized from miR-17-92 cluster host gene due to pre-miRNA processing, and is referred as miRNA-host gene lncRNA (lnc-miRHG). Until now, the biologic function of most lnc-miRHGs in tumor progression is not well understood. This study aimed to investigate the expression and clinical significance of MIR17HG in colon cancer.
Methods: Quantitative real-time PCR analysis was used to evaluate MIR17HG expression in colon cancer tissues and paired adjacent normal mucosa. The levels of miR-17-92 cluster and important components of Wnt/β-catenin signaling pathway were also explored. Cell biology assays were used to investigate biologic consequences of MIR17HG in regulating cell proliferation, colony formation and invasion, as well as the roles in regulating epithelial-mesenchymal transition (EMT). Moreover, a colon tumor xenograft model was established to explore the in vivo effect of MIR17HG on cell proliferation.
Results: Expression of MIR17HG was found to be elevated in colon cancer (P<0.001). Upregulation of MIR17HG was significantly correlated with lymph node metastasis (P=0.005) and TNM stage (P<0.001), and also an independent prognostic indicator of overall survival and disease-free survival in colon cancer patients. Suppression of MIR17HG inhibited colon cancer cell viability, invasion, and EMT process, and significantly reduced the ability of the cells to form tumors in vivo. Moreover, miR-17 and miR-18a, two key components of miR-17-92 cluster, were suppressed after knockdown of MIR17HG. Furthermore, the Wnt/β-catenin signaling, activated by miR-17 and miR-18a, was required for the oncogenic role of MIR17HG in colon cancer.
Conclusions: MIR17HG mediated upregulation of miR-17 and miR-18a promotes the progression of colon cancer via activating Wnt/β-catenin signaling.