Circ_DOCK1 regulates USP11 through miR-132-3p to control colorectal cancer progression

Abstract

Background Circular RNAs (circRNAs) take part in colorectal cancer malignancies. CircRNA dedicator of cytokinesis 1 (circ_DOCK1) is involved in colorectal cancer progression, but the mechanism underlying this circRNA that takes part in colorectal cancer development remains largely undetermined. Methods Tumor and normal para-cancerous tissues were collected from 42 colorectal cancer patients. Human colorectal cancer cell lines (HCT116 and SW480) were used for the experiments in vitro. Circ_DOCK1, microRNA (miR)-132-3p, and ubiquitin-specific protease 11 (USP11) levels were measured through quantitative real-time polymerase chain reaction and Western blotting. Cell growth, metastasis, and apoptosis were investigated via colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, MTT, flow cytometry, Western blotting, and transwell analyses. The target association was evaluated via dual-luciferase reporter analysis, RNA pull-down, and immunoprecipitation (RIP). Xenograft assay was performed using HCT116 cells. USP11 and Ki67 levels in tumor tissues were detected via immunohistochemistry. Results Circ_DOCK1 expression was enhanced in colorectal cancer tissues and cells. Silencing circ_DOCK1 repressed cell growth, migration, and invasion, and facilitated apoptosis. Circ_DOCK1 sponged miR-132-3p, and miR-132-3p silence mitigated the effect of circ_DOCK1 interference on cell growth, metastasis, and apoptosis. MiR-132-3p targeted USP11, and circ_DOCK1 could regulate USP11 level by miR-132-3p. MiR-132-3p suppressed cell growth, metastasis, and apoptosis, and USP11 attenuated these effects. Knockdown of circ_DOCK1 decreased colorectal cancer cell xenograft tumor growth. Conclusion Circ_DOCK1 interference suppressed cell growth and metastasis, and increased apoptosis of colorectal cancer via decreasing USP11 by increasing miR-132-3p.

miRNA-mRNA Regulatory Network Reveals miRNAs in HCT116 in Response to Folic Acid Deficiency via Regulating Vital Genes of Endoplasmic Reticulum Stress Pathway

“…MiR-218-5p is thought to be tumor suppressive and capable of negatively regulating DPH1 in CRC cells [ 38 ]. MiR-132-3p was demonstrated to be downregulated in CRC tissues and cells [ 39 ], which has been reported to be a molecular marker to predict CRC resistance to 5-Fluorouracil-based chemotherapy [ 40 ] and usefully constrains cell growth and metastasis in CRC cells [ 41 ]. MiR-379-5p is generally considered to be a tumor suppressor to directly suppress the EMT, proliferation, migration, and invasion of carcinoma cells in multiple tumor [ 42 , 43 ]; however, there is little research on its role in CRC.…”

The Dual Role of USP11 in Cancer

“…Finally, the USP11/PPP1CA complex promotes the progression of colorectal cancer by activating the ERK/MAPK signaling pathway [ 33 ]. Another study also found that circ_DOCK1 inhibits the progression of colorectal cancer by targeting miR-132-3p to interfere with the expression of USP11 [ 34 ]. Taken together, these results suggest that USP11 is involved in the occurrence and development of colorectal cancer.…”

Ubiquitin specific peptidase 11 as a novel therapeutic target for cancer management

“…Intriguingly, the activity of USP11 could be phosphorylated by FASN-induced PI3K-S6 kinase signaling, and phosphorylated USP11 further enhances its interaction with eIF4B and thereby promoting oncogenic translation [ 37 ], implying that the activity of deubiquitinase USP11 is also activated by the kinase and enriches the complex regulatory network of USP11. Weitong Zhang et al [ 38 ] found that Circ_DOCK1 interference suppressed USP11 by increasing miR-132-3p, thereby inhibiting cell growth and metastasis and increasing apoptosis in colorectal cancer, which further identified the novel interaction between miRNA and USP11. The above results demonstrate that USP11, a typical deubiquitinase, regulates the state and stability of multiple proteins via several manners.…”