Background Colorectal cancer (CRC) poses a heavy threat to human health owing to its high incidence and mortality. Circular RNAs (circRNAs) were investigated to participate in the progression of CRC, whereas there was no revenant data on the CRC process regulated by hsa_circ_0000231. This study aimed to explore the effects of hsa_circ_0000231 on CRC progression and underneath regulatory mechanism. Methods The expression levels of hsa_circ_0000231, miR-502-5p, and Myosin VI (MYO6) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). Western blot was employed to determine the protein expression levels of MYO6 and proliferating cell nuclear antigen (PCNA). The effects of hsa_circ_0000231 on cell proliferation, apoptosis, migration, and invasive in CRC were determined by cell counting kit-8 proliferation (CCK-8) and colony formation assays, flow cytometry analysis, wound-healing assay, and transwell invasion assay, respectively. Glucose uptake and lactate production were severally illustrated by glucose assay kit and lactate assay kit. The relationship between miR-502-5p and hsa_circ_0000231 or MYO6 was predicted by circular RNA interactome or targetScan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo tumor formation assay was carried out to determine the effects of hsa_circ_0000231 knockdown on tumor growth in vivo. Results Hsa_circ_0000231 expression was dramatically upregulated while miR-502-5p was obviously downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0000231 knockdown repressed the expression levels of MYO6 and PCNA protein. Functionally, hsa_circ_0000231 knockdown repressed cell glycolysis, proliferation, migration and invasion, and induced cell apoptosis, whereas these effects were decreased by miR-502-5p inhibitor. Mechanistically, hsa_circ_0000231 acted as a sponge of miR-502-5p and miR-502-5p bound to MYO6. Furthermore, hsa_circ_0000231 knockdown decreased tumor volume and weight of CRC in vivo. Conclusion Hsa_circ_0000231 knockdown inhibited CRC progression and glycolysis by downregulating MYO6 expression through sponging miR-502-5p, which might provide a theoretical basis in further studying circ_0000231-directed therapy in CRC.
Colorectal cancer (CRC) is the third most common type of cancer worldwide. Currently, surgery, chemotherapy and radiation therapy are the conventional approaches used to treat CRC. However, these therapy strategies cause several side effects. The present study aimed to develop an alternative and more effective treatment approach for patients with CRC. It has been reported that salt-inducible kinase 2 (SIK2) acts as an oncogene. Therefore, in the present study, the expression levels of SIK2 were determined in CRC cells using western blot analysis and reverse transcription-quantitative PCR. In addition, SIK2 was knocked down in CRC cells to evaluate its role in cell proliferation, migration, invasion and glycolysis using Cell Counting Kit-8, wound healing, Transwell assays and glycolysis cell-based assay kit, respectively. Additionally, the target genes of SIK2 were identified using bioinformatics analysis, while SIK2 overexpression experiments were carried out to determine whether SIK2 could regulate CRC cell malignant behavior and glycolysis. The results revealed that SIK2 was upregulated in CRC cells. Furthermore, SIK2 knockdown attenuated CRC cell proliferation, migration, invasion and glycolysis. Bioinformatics analysis predicted that SIK2 could interact with tripartite motif containing 28 (TRIM28), while TRIM28 overexpression could reverse the effects of SIK2 silencing on cell proliferation, migration, invasion and glycolysis. This finding indicated that the aforementioned effects of SIK2 were mediated by regulating TRIM28. In conclusion, the findings of the present study suggested that SIK2 may be involved in CRC carcinogenesis and glycolysis by regulating TRIM28 expression. These findings could provide a novel approach to targeted therapy and clinical diagnosis of CRC in the future.
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