Knockdown of Uba2 inhibits colorectal cancer cell invasion and migration through downregulation of the Wnt/β‐catenin signaling pathway

Abstract

Colorectal cancer is a serious threat to human health, and has a high mortality rate. There is currently no effective therapy for end-stage colorectal cancer. In recent years, molecular targeted therapy has received increasing attention for cancer treatment. In particular, the role of Uba2, a vital component of SUMO-activating enzyme, has been highlighted, which plays important roles in the progression of certain cancers; however, its role in colorectal cancer remains unclear. Accordingly, the aim of this study was to evaluate the relationship between Uba2 and colorectal cancer. Uba2 expression was knocked down in two colorectal cancer cell lines, and gene microarray analysis was conducted, followed by proliferation, migration, and invasion assays. Uba2 knockdown influenced the expression of several genes, and significantly inhibited the proliferation, migration, and invasion of cancer cells. To determine the underlying mechanism, the expression of related signaling pathways and molecules was evaluated in the knockdown cell lines. Overall, the results suggest that Uba2 participates in the progression, invasion, and metastasis of colorectal cancer, and the possible mechanism is via regulating the Wnt signaling pathway and enhancing epithelial-mesenchymal transition behaviors of colorectal cancer cells. Therefore, Uba2 is expected to be an important oncoprotein and potential therapeutic target in colorectal cancer.

Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer

“…For over-expression studies, the Uba2 gene was synthesized according to the human UBA2 mRNA sequence and inserted into a lentiviral vector (Genechem). Transfection was carried out as previously described[ 15 ]. BGC-823 cells were infected with siUba2 or siNC lentivirus at a multiplicity of infection of 100.…”

“…Recent studies have shown that the proteins involved in the SUMO system could regulate carcinogenesis-related processes, such as cell growth, differentiation, senescence, oxidative stress, and apoptosis[ 12 ]. As an essential component of SUMO-activating enzyme E1, ubiquitin-like modifier activating enzyme 2 (Uba2) is over-expressed in many malignancies, including liver cancer[ 13 ], small cell lung cancer[ 14 ], colorectal cancer[ 15 ], and GC[ 16 ]. Besides, knock-down of Uba2 suppresses certain malignancies.…”

“…Besides, knock-down of Uba2 suppresses certain malignancies. Uba2 level is correlated with the Wnt/β-catenin pathway in colorectal cancer[ 15 ]; however, its role in GC remains unclear.…”

Monensin inhibits proliferation, migration, and promotes apoptosis of breast cancer cells via downregulating UBA2

“…UBA2 has also been proved to play a role in promoting cancer. UBA2 knockdown can affect the expression of several cancer-related genes and significantly inhibit the proliferation, migration, and invasion of colorectal cancer cells (Cheng et al, 2018).…”

“…UBA2 is a key component of small ubiquitin related modifier (SUM0) activating enzyme and is the first step in mediating the modification of SUMO. Studies have shown that UBA2 is overexpressed in a variety of tumors and is closely related to the occurrence, development, and prognosis of tumors (Cheng et al, 2018;Lapaquette et al, 2017). Through gene sequencing, Maguire et al (Maguire et al, 2016)found that the expression of UBA2 in breast cancer was abnormal, indicating that UBA2 might be used as a drug therapeutic target.…”