Effects of CircMGAT5 Downregulation on Invasion and MMP-2 Expression in Ovarian Cancer Cells
Abstract
Objective: To elucidate the regulatory effects and mechanisms of circular RNA MGAT5 (circMGAT5) on the invasive ability of human ovarian cancer (OC) cells. Methods: Human OC SKOV-3 cells were transfected with circMGAT5 interference plasmids. The expression level of circMGAT5 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation and invasive abilities of cancer cells were determined using soft agar colony formation assay and Transwell assay, respectively. The expression of matrix metalloproteinase-2 (MMP-2) at mRNA and protein levels was detected by qRT-PCR and immunofluorescence, respectively. Results: CircMGAT5 level in the circMGAT5-transfected group was significantly downregulated in a concentration- and time-dependent manner (p < 0.005). Soft agar colony formation assay exhibited that the number of colonies formed in the 6.25, 12.5, and 25.0 nM siRNA groups was significantly reduced in a concentration-dependent manner (p < 0.005). Transwell assay revealed that the number of cells penetrating the filter membrane in the 6.25, 12.5, and 25.0 nM siRNA groups was significantly decreased in a concentration-dependent manner (p < 0.005). qRT-PCR and immunofluorescence results demonstrated that the mRNA and protein levels of MMP-2 in OC cells of the siRNA-transfected group were significantly decreased. Conclusion: circMGAT5 plays an important role in the invasion of OC cells, and its mechanism may be related to the downregulation of MMP-2 expression.
References
Cabasag C, Fagan P, Ferlay J, et al., 2022, Ovarian Cancer Today and Tomorrow: A Global Assessment by World Region and Human Development Index Using GLOBOCAN 2020. International Journal of Cancer, 151(9): 1535–1541.
Valadi H, Ekström K, Bossios A, et al., 2007, Exosome-Mediated Transfer Of mRNAs and microRNAs Is a Novel Mechanism of Genetic Exchange Between Cells. Nature Cell Biology, 9(6): 654–659.
Ye H, Wang R, Yu X, et al., 2023, Exosomal CircNFIX Promotes Angiogenesis in Ovarian Cancer Via miR-518a-3p/TRIM44 Axis. Kaohsiung Journal of Medical Sciences, 39(1): 26–39.
Ma R, Ye X, Cheng H, et al., 2021, Tumor-Derived Exosomal CircRNA051239 Promotes Proliferation and Migration of Epithelial Ovarian Cancer. American Journal of Translational Research, 13(3): 1125–1139.
Luo Y, Gui R, 2020, Circulating Exosomal circFoxp1 Confers Cisplatin Resistance in Epithelial Ovarian Cancer Cells. Journal Of Gynecologic Oncology, 31(5): e75.
Wu Y, Xu M, Feng Z, et al., 2023, AUF1-Induced Circular RNA hsa_circ_0010467 Promotes Platinum Resistance of Ovarian Cancer Through miR-637/LIF/STAT3 Axis. Cellular And Molecular Life Sciences, 80(9): 256.
Hansen T, Jensen T, Clausen B, et al., 2013, Natural RNA Circles Function as Efficient MicroRNA Sponges. Nature, 495(7441): 384–388.
Xu W, Zhu L, Zhang S, et al., 2025, Advances in The Roles and Molecular Mechanisms of Exosomal Circular RNAs In Regulating the Pre-Metastatic Niche of Tumors. Discover Oncology, 16(1): 568.
Chen Z, Wang C, Ding J, et al., 2024, Construction and Analysis of Competitive Endogenous RNA Networks and Prognostic Models Associated with Ovarian Cancer Based on the exoRBase Database. PLoS One, 19(4): e0291149.
He L, Man C, Xiang S, et al., 2021, Circular RNAs’ Cap-Independent Translation Protein and Its Roles in Carcinomas. Molecular Cancer, 20(1): 119.
Conn V, Chinnaiyan A, Conn S, 2024, Circular RNA In Cancer. Nature Reviews Cancer, 24(9): 597–613.
Wang X, Yao Y, Jin M, 2020, Circ-0001068 Is A Novel Biomarker for Ovarian Cancer and Inducer of PD1 Expression in T Cells. Aging (Albany NY), 12(19): 19095–19106.
Luo Y, Gui R, 2020, Circulating Exosomal circFoxp1 Confers Cisplatin Resistance in Epithelial Ovarian Cancer Cells. Journal Of Gynecologic Oncology, 31(5): e75.
Ma R, Ye X, Cheng H, et al., 2021, Tumor-Derived Exosomal circRNA051239 Promotes Proliferation and Migration of Epithelial Ovarian Cancer. American Journal of Translational Research, 13(3): 1125–1139.
Fan Y, Zhang Y, Wu Y, et al., 2008, Inhibition of Signal Transducer and Activator of Transcription 3 Expression by RNA Interference Suppresses Invasion Through Inducing Anoikis in Human Colon Cancer Cells. World Journal of Gastroenterology, 14(3): 428–434.
So K, Min K, Hong J, et al., 2015, Interleukin-6 Expression by Interactions Between Gynecologic Cancer Cells and Human Mesenchymal Stem Cells Promotes Epithelial-Mesenchymal Transition. International Journal of Oncology, 47(4): 1451–1459.
Zhao X, Wang X, Wang C, et al., 2025, SOX15 Transcriptionally Decreases the Level of MMP2 And Inhibits Vasculogenic Mimicry to Slow Down the Progression of Ovarian Cancer. Biology Of the Cell, 117(8): e70031.
Momen Razmgah M, Ghahremanloo A, Javid H, et al., 2022, The Effect of Substance P And Its Specific Antagonist (Aprepitant) On the Expression Of MMP-2, MMP-9, VEGF, And VEGFR In Ovarian Cancer Cells. Molecular Biology Reports, 49(10): 9307–9314.
Begum Y, Pandit A, Shukla D, et al., 2025, Suppression of Endometriosis By miRNA-34a Via Inhibition of Matrix Metalloproteinase-2: An Alternative Pathway to Impede Invasion. Noncoding RNA Research, 12: 92–101.
Escalona R, Chu S, Kadife E, et al., 2022, Knock Down Of TIMP-2 By siRNA and CRISPR/Cas9 Mediates Diverse Cellular Reprogramming of Metastasis and Chemosensitivity in Ovarian Cancer. Cancer Cell International, 22(1): 422.
