J Gynecol Oncol.  2023 Mar;34(2):e19. 10.3802/jgo.2023.34.e19.

CircSMAD2 accelerates endometrial cancer cell proliferation and metastasis by regulating the miR-1277-5p/MFGE8 axis

• Wu Y
• Wang F
• Shi J
• Guo X
• Li F

• KMID: 2552519
• DOI: http://doi.org/10.3802/jgo.2023.34.e19

Abstract

Objective
Endometrial cancer (EC) is a common gynecological malignant tumor. CircRNAs play crucial roles in cancer progression and metastasis. However, the biological functions of circRNAs in EC remain largely unknown.
Methods
CircSMAD2, miR-1277-5p, MFGE8 and relative maker protein expression in EC tissues or cell lines were analyzed by quantitative real-time polymerase chain reaction and Western blot. In vitro and in vivo functional assays, including EDU, CCK8, colony formation, transwell, tube formation and tumor xenograft assays, were conduct to explore the effects of circSMAD2 on EC. Mechanism assays were conducted to confirm the binding between miR-1277-5p and circSMAD2 or MFGE8 expression.
Results
Upregulation of circSMAD2 was uncovered in both EC tissues and cell lines. Functionally, silencing of circSMAD2 apparently inhibited the proliferation, migration, invasion and angiogenesis of EC cell lines in vitro. Mechanistically, circSMAD2 sponged miR-1277-5p to upregulate MFGE8 expression. The decrease of miR-1277-5p and increase of MFGE8 were observed both in EC tissues and cell lines. Then MFGE8 knockdown or miR-1277-5p upregulation suppressed EC cell oncogenic biological behavior. Rescue experiments showed that miR-1277-5p mimics countervailed the anticancer effects of circSMAD2 silencing on EC. Besides that, MFGE8 overexpression also attenuated the inhibitory action of miR-1277-5p mimic in EC. Moreover, knockdown of circSMAD2 inhibited EC growth in vivo.
Conclusion
CircSMAD2 functions as an oncogene in promoting the progression of EC through miR-1277-5p/MFGE8 axis.

Keyword

Circular RNA SMAD Family Member 2; MicroRNA-1277-5p; Milk Fat Globule Epidermal Growth Factor 8; Endometrial Cancer