Abstract
Background
Circular RNAs (circRNAs) are involved in a variety of biological processes, including tumorigenesis. However, the exact role and molecular mechanisms of circ_0000043 in endometrial carcinoma (EC) remain largely unknown.
Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the expression levels of circ_0000043, microRNA-1271-5p (miR-1271-5p) and catenin delta 1 (CTNND1). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to measure cell proliferation, cell apoptosis and cell cycle distribution, respectively. Cell migration and invasion were assessed by transwell assay. Western blot assay was performed to examine the protein expression of matrix metalloproteinase 2 (MMP2), MMP9 and CTNND1. The interaction between miR-1271-5p and circ_0000043 or CTNND1 was predicted by starBase and confirmed by dual-luciferase reporter assay. The mice xenograft model was established to investigate the role of circ_0000043 in vivo.
Results
Circ_0000043 and CTNND1 were highly expressed and miR-1271-5p was lowly expressed in EC tissues and cells. Knockdown of circ_0000043 inhibited the progression of EC by inhibiting cell proliferation, migration, invasion and tumor growth (in vivo) and promoting apoptosis. MiR-1271-5p was a direct target of circ_0000043 and its inhibition reversed the inhibitory effect of circ_0000043 knockdown on the progression of EC cells. In addition, CTNND1 was a downstream target of miR-1271-5p, and miR-1271-5p overexpression inhibited EC cell proliferation, migration and invasion and induced apoptosis by targeting CTNND1. Moreover, circ_0000043 positively regulated CTNND1 expression by sponging miR-1271-5p.
Conclusion
Circ_0000043 knockdown inhibited the progression of EC by regulating miR-1271-5p/CTNND1 axis, which might provide a promising circRNA-targeted therapy for EC.
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DW, MT, WF: conception and design; analysis and interpretation of data; drafting of article; revising article critically for important intellectual content; final approval of version to be published; agree to be accountable for all aspects of the work. XZ, XZ: analysis and interpretation of data; drafting of article; final approval of version to be published; agree to be accountable for all aspects of the work. YC: interpretation of data; revising article critically; final approval of version to be published; agree to be accountable for all aspects of the work. SZ: analysis and interpretation of data; drafting of article; revising article critically for important intellectual content; final approval of version to be published; agrees to be accountable for all aspects of the work.
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Wei, D., Tian, M., Fan, W. et al. Circular RNA circ_0000043 promotes endometrial carcinoma progression by regulating miR-1271-5p/CTNND1 axis. Arch Gynecol Obstet 303, 1075–1087 (2021). https://doi.org/10.1007/s00404-020-05849-z
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DOI: https://doi.org/10.1007/s00404-020-05849-z