Circular RNA circDNM3OS Functions as a miR-145-5p Sponge to Accelerate Cholangiocarcinoma Growth and Glutamine Metabolism by Upregulating MORC2

Background: Cholangiocarcinoma (CCA) is the second most common liver malignant tumor. CircRNA hsa_circ_0005230 (circDNM3OS) has been reported to exert an oncogenic role in CCA. However, the mechanisms related to circDNM3OS in CAA progression have not been fully elucidated. Methods: The expression of circDNM3OS, microRNA (miR)-145-5p, and MORC2 (MORC Family CW-Type Zinc Finger 2) mRNA were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8), colony formation, transwell, wound-healing, and flow cytometry assays. The levels of glutamine, alpha-KG (alpha-ketoglutarate), and ATP (adenosine triphosphate) were detected using commercial kits. The relationship between circDNM3OS or MORC2 and miR-145-5p was verified by dualluciferase reporter and/or RNA immunoprecipitation (RIP) assays. Protein level of MORC2 was measured by Western blotting. The role of circDNM3OS in CCA growth was verified by xenograft experiment. Results: CircDNM3OS and MORC2 were upregulated while miR-145-5p was downregulated in CCA tissues and cells. Inhibition of circDNM3OS reduced xenograft tumor growth in vivo and constrained proliferation, colony formation, migration, invasion, induced apoptosis, and reduced glutamine metabolism of CCA cells in vitro. CircDNM3OS sponged miR-145-5p to elevate MORC2 expression. MiR-145-5p silencing overturned circDNM3OS knockdown-mediated influence on malignancy and glutamine metabolism of CCA cells. Also, MORC2 overexpression reversed the repressive impact of miR-145-5p mimic on malignancy and glutamine metabolism of CCA cells. Conclusion: CircDNM3OS facilitates CCA growth and glutamine metabolism by regulating the miR-145-5p/MORC2 pathway, offering a novel mechanism to understand the progression of CCA.

Automated summary

The study revealed that circDNM3OS promotes CCA growth and glutamine metabolism by regulating the miR-145-5p/MORC2 pathway, with experimental evidence supporting this conclusion.