Circular RNA CUL2 regulates the development of colorectal cancer by modulating apoptosis and autophagy via miR-208a-3p/PPP6C

Bin-Lin Yang,Xiao-Hui Li,Guo-Qiang Liu,Ping Li

doi:10.18632/aging.203827

Bin-Lin Yang, Xiao-Hui Li + Show 2 more

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https://doi.org/10.18632/aging.203827

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Abstract

Aim: To explore the function of circular RNA CUL2 (circCUL2) in colorectal cancer progression.Method: RT-PCR was carried out to detect the expression of circCUL2 in colorectal cancer tissues and cell lines. Western blot and immunofluorescence were used to determine the level of autophagy. CCK-8, clone formation assay, and EdU staining were used to assess the proliferation ability. Luciferase assay verified the relationship between miR-208a-3p and circCUL2 /PPP6C. The xenograft mouse model was used to confirm the function of circCUL2 in vivo.Results: The expression level of circCUL2 was down-regulated in colorectal cancer tissues and cell lines. Forcing expression of circCUL2 inhibited proliferation ability, induced apoptosis, and autophagy in colorectal cancer cells. Luciferase assay verified that miR-208a-3p could bind with circCUL2/PPP6C. Overexpression of circCUL2 could inhibit cancer progression via targeting the miR-208a-3p/PPP6C signal pathway.Conclusion: CircCUL2 participates in progression via the miR-208a-3p/PPP6C axis in colorectal cancer. CircCUL2 would be an underlying target for the diagnosis and therapy of colorectal cancer.

Highlights

Colorectal cancer (CRC) is the third most common cancer in the world and the fourth leading cause of cancer death in the world [1, 2]
We cultured CRC cell lines (HT290, HCT116, SW480, SW620), qRTPCR assay results performed the down-regulated circCUL2 level in CRC cell lines compared with FHC cells (Figure 1C)
We first designed two sets of primers for circCUL2: convergent primers that were expected to amplify only the linear form, CUL2 mRNA, and divergent primers to amplify only the circular form, circCUL2. cDNA and genomic DNA were used as templates, and the specificity of the qRT-PCR was validated by 1% agarose gel electrophoresis

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer in the world and the fourth leading cause of cancer death in the world [1, 2]. In terms of its incidence, it accounts for almost 10% of a global cancer diagnosis. It ranks third in males and second in females. Many patients in developed countries can be diagnosed early in the disease. There is a higher mortality rate among patients diagnosed in developing areas [3]. CRC has a high incidence in a large number of people who are sedentary and high-fat diet [4], so it is considered to be a lifestyle-related disease. In view of the high morbidity, high mortality, and low cure rate of CRC, it is of high research value to explore the effective therapeutic targets of CRC

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