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Circ_0002577/miR-126-5p/MACC1 axis promotes endometrial carcinoma progression by regulation of proliferation, migration, invasion, and apoptosis of endometrial carcinoma cells

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

Endometrial carcinoma (EC) is a common female reproductive malignant tumor. Circular RNAs (circRNAs) have been reported to participate in tumorigenesis, including EC. Therefore, this study was designed to clarify the role and underlying molecular mechanisms of circ_0002577 in EC.

Methods

The expression levels of circ_0002577, miR-126-5p, and metastasis associated in colon cancer 1 (MACC1) was determined by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The protein expression was quantified by western blot assay. The proliferation of EC cells was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony-forming assays. The migration and invasion of EC cells was measured by transwell assay. The apoptosis was determined by flow cytometry assay. Dual-luciferase reporter assay and RNA pull-down assays were performed to confirm the relationship between miR-126-5p and circ_0002577 or MACC1. The influence of circ_0002577 inhibition on tumor growth was assessed by xenograft experiment.

Results

Circ_0002577 and MACC1 were increased while miR-126-5p was decreased in EC tissues and cells. Loss-of-functional experiment revealed that silencing of circ_0002577 inhibited the proliferation, migration, and invasion while induced apoptosis of EC cells, which were overturned by overexpression of MACC1. The upregulation of miR-126-5p also impeded proliferation and mobility while induced apoptosis of EC cells. MiR-126-5p, negatively regulating MACC1 expression, was a functional target of circ_0002577 in EC cells. Moreover, we also confirmed that suppression of circ_0002577 repressed tumor growth in vivo.

Conclusion

The contributions of the circ_0002577 in EC were contributed to its interactions with miR-126-5p and MACC1, which offered a new perspective to the roles of circ_0002577 in EC.

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References

  1. Sorosky JI (2012) Endometrial cancer. Obstet Gynecol 120(2 Pt 1):383–397

    Article  Google Scholar 

  2. Genestie C, Leary A, Devouassoux M et al (2017) Histological and molecular classification of endometrial carcinoma and therapeutical implications. Bull Cancer 104(12):1001–1012

    Article  Google Scholar 

  3. Ali AT (2013) Risk factors for endometrial cancer. Ceska Gynekol 78(5):448–459

    PubMed  Google Scholar 

  4. Holland CM (2008) The role of radical surgery in carcinoma of the endometrium. Clin Oncol (R Coll Radiol) 20(6):448–456

    Article  CAS  Google Scholar 

  5. Memczak S, Jens M, Elefsinioti A et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333–338

    Article  CAS  Google Scholar 

  6. Li J, Yang J, Zhou P et al (2015) Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am J Cancer Res 5(2):472–480

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Ruan H, Xiang Y, Ko J et al (2019) Comprehensive characterization of circular RNAs in ~ 1000 human cancer cell lines. Genome Med 11(1):55

    Article  Google Scholar 

  8. Wang H, Yan X, Zhang H et al (2019) CircRNA circ_0067934 overexpression correlates with poor prognosis and promotes thyroid carcinoma progression. Med Sci Monit 25:1342–1349

    Article  CAS  Google Scholar 

  9. Zhang B, Pan X, Cobb GP et al (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302(1):1–12

    Article  CAS  Google Scholar 

  10. Vishnoi A, Rani S (2017) MiRNA biogenesis and regulation of diseases: an overview. Methods Mol Biol 1509:1–10

    Article  CAS  Google Scholar 

  11. Li S, Zhang J, Wan X (2015) Role of miRNAs in endometrial cancer. Histol Histopathol 30(5):539–548

    CAS  PubMed  Google Scholar 

  12. Liu Y, Chang Y, Cai Y (2020) Hsa_circ_0061140 promotes endometrial carcinoma progression via regulating miR-149–5p/STAT3. Gene 745:144625

    Article  CAS  Google Scholar 

  13. Lin A, Zhang RL, Zhang X et al (2019) Significance of plasma MACC1 levels on the prognostic stratification in patients with colorectal cancer. J Cell Mol Med 23(2):1598–1601

    Article  CAS  Google Scholar 

  14. Tong G, Cheng B, Li J et al (2019) MACC1 regulates PDL1 expression and tumor immunity through the c-Met/AKT/mTOR pathway in gastric cancer cells. Cancer Med 8(16):7044–7054

    Article  CAS  Google Scholar 

  15. Link T, Kuhlmann JD, Kobelt D et al (2019) Clinical relevance of circulating MACC1 and S100A4 transcripts for ovarian cancer. Mol Oncol 13(5):1268–1279

    Article  CAS  Google Scholar 

  16. Peng T, Li Z, Li D et al (2019) MACC1 promotes angiogenesis in cholangiocarcinoma by upregulating VEGFA. Onco Targets Ther 12:1893–1903

    Article  CAS  Google Scholar 

  17. Zhou X, Xu CJ, Wang JX et al (2015) Metastasis-associated in colon cancer-1 associates with poor prognosis and promotes cell invasion and angiogenesis in human cervical cancer. Int J Gynecol Cancer 25(8):1353–1363

    Article  Google Scholar 

  18. Qi X, Zhang DH, Wu N et al (2015) ceRNA in cancer: possible functions and clinical implications. J Med Genet 52(10):710–718

    Article  Google Scholar 

  19. Grillone K, Riillo C, Scionti F et al (2020) Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter.” J Exp Clin Cancer Res 39(1):117

    Article  CAS  Google Scholar 

  20. Ferlita A, Battaglia R, Andronico F et al (2018) Non-coding RNAs in endometrial physiopathology. Int J Mol Sci. https://doi.org/10.3390/ijms19072120

    Article  PubMed  PubMed Central  Google Scholar 

  21. Xu H, Gong Z, Shen Y et al (2018) Circular RNA expression in extracellular vesicles isolated from serum of patients with endometrial cancer. Epigenomics 10(2):187–197

    Article  CAS  Google Scholar 

  22. Shen Q, He T, Yuan H (2019) Hsa_circ_0002577 promotes endometrial carcinoma progression via regulating miR-197/CTNND1 axis and activating Wnt/beta-catenin pathway. Cell Cycle 18(11):1229–1240

    Article  CAS  Google Scholar 

  23. Sun Z, Ou C, Liu J et al (2019) YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer. Oncogene 38(14):2627–2644

    Article  CAS  Google Scholar 

  24. Liu S, Gao S, Wang XY et al (2012) Expression of miR-126 and Crk in endometriosis: miR-126 may affect the progression of endometriosis by regulating Crk expression. Arch Gynecol Obstet 285(4):1065–1072

    Article  CAS  Google Scholar 

  25. Liu B, Li J, Cairns MJ (2014) Identifying miRNAs, targets and functions. Brief Bioinform 15(1):1–19

    Article  Google Scholar 

  26. Wang C, Zhou B, Liu M et al (2017) miR-126-5p restoration promotes cell apoptosis in cervical cancer by targeting Bcl2l2. Oncol Res 25(4):463–470

    Article  Google Scholar 

  27. Wu G, Cao L, Zhu J et al (2019) Loss of RBMS3 confers platinum resistance in epithelial ovarian cancer via activation of miR-126-5p/beta-catenin/CBP signaling. Clin Cancer Res 25(3):1022–1035

    Article  CAS  Google Scholar 

  28. Meng X, Liu J, Wang H et al (2019) MicroRNA-126–5p downregulates BCAR3 expression to promote cell migration and invasion in endometriosis. Mol Cell Endocrinol 494:110486

    Article  CAS  Google Scholar 

  29. Zhang Q, Xu P, Lu Y et al (2018) Correlation of MACC1/c-Myc expression in endometrial carcinoma with clinical/pathological features or prognosis. Med Sci Monit 24:4738–4744

    Article  CAS  Google Scholar 

  30. Chen S, Zong ZH, Wu DD et al (2017) The role of metastasis-associated in colon cancer 1 (MACC1) in endometrial carcinoma tumorigenesis and progression. Mol Carcinog 56(4):1361–1371

    Article  CAS  Google Scholar 

  31. Ding Y, Li X, Hong D et al (2016) Silence of MACC1 decreases cell migration and invasion in human malignant melanoma through inhibiting the EMT. Biosci Trends 10(4):258–264

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Gynaecology, Shaanxi Provincial People’s Hospital, No. 256, Youyi West Road, Xi’an City, 710000, Shaanxi Province, China

    Wenzhi Wang, Wen Jin & Xiaoying Liu

  2. College of Pharmacy, Xi’an Medical University, Xi’an, Shaanxi, China

    Lei Zheng

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  1. Wenzhi Wang
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  2. Wen Jin
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  3. Xiaoying Liu
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Correspondence to Wenzhi Wang.

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Wang, W., Jin, W., Liu, X. et al. Circ_0002577/miR-126-5p/MACC1 axis promotes endometrial carcinoma progression by regulation of proliferation, migration, invasion, and apoptosis of endometrial carcinoma cells. Arch Gynecol Obstet 306, 481–491 (2022). https://doi.org/10.1007/s00404-022-06412-8

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  • DOI: https://doi.org/10.1007/s00404-022-06412-8

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