Abstract
Cervical cancer (CC) is one of the most common cancers that threaten the life of women. More and more circular RNAs (circRNAs) have been found to be maladjusted in tumor tissues. However, the mechanism of circ_TMCO3 in CC needs to be studied. In this study, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry (IHC) were used to detect the expressions of circ_TMCO3, miR-1291, and FERM domain-containing protein 6 (FRMD6). Cell viability, proliferation, apoptosis, migration, invasion, and protein level were detected via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2’-deoxyuridine (EdU), flow cytometry, transwell and western blot, respectively. The glycolysis level was detected via specific kits. Dual-luciferase activity assay was used to analyze the targeted relationship between miR-1291 and circ_TMCO3 or FRMD6. Xenograft models were used to analyze the effect of circ_TMCO3 on the growth of CC tumors in vivo. Circ_TMCO3 and FRMD6 were low expressed in tumor tissues, and miR-1291 was conspicuously upregulated in tumor tissues. Upregulation of circ_TMCO3 dramatically curbed cell viability, proliferation, migration, and invasion, and enhanced cell apoptosis, while those effects were attenuated after the overexpression of miR-1291. MiR-1291 could directly target FRMD6, and knockdown of FRMD6 could restore the inhibitory effect of miR-1291 silencing on tumor cell growth. In terms of mechanism, circ_TMCO3 was confirmed as a miR-1291 sponge to regulate the expression of FRMD6. Tumor growth was markedly retarded with the overexpression of circ_TMCO3. In conclusion, circ_TMCO3 inhibited tumorigenicity of CC via miR-1291/FRMD6 axis, providing a potential therapeutic strategy for CC patients.
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The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
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This study was supported by the Free Exploration and Innovation Project of the First Affiliated Hospital of Xi’an Jiaotong University (Award Number: 2020ZYTS-09).
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Xue Xue and Yixia Pan designed and performed the research. Xue Xue and Chen Li collected the data for statistical analysis and chart plotting. Xue Xue wrote the manuscript and Chen Li is responsible for checking. All authors read and approved the final manuscript.
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Xue, X., Pan, Y. & Li, C. Circ_TMCO3 Inhibits the Progression of Cervical Cancer by Activating FRMD6 Expression by Restraining miR-1291. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01549-0
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DOI: https://doi.org/10.1007/s43032-024-01549-0