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| CiRS-7 Enhances Endometrial Cancer Cell Resistance to ER Stress by Inhibiting MiR-7 Expression |
| AN Xin, et al |
| The First Hospital of Handan, Hebei Handan 056002, China |
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Abstract Objective: To explore the relationship between circular RNA CiRS-7 and endoplasmic reticulum (ER) stress in endometrial carcinoma (EC) cells. Methods: An EC cell line, Ishikawa, was stably transfected with ciRS-7 using lentiviral vectors. Ishikawa cells' proliferation activity, scratch wound healing, migration ability, and invasion capability were assessed. QRT-PCR determined miR-7 expression levels in these cells. Ishikawa cells were serum-starved for 24 hours, and the expression levels of ER stress-related and apoptosis-related proteins were measured by Western blot, with miR-7 expression quantified by qRT-PCR. Intracellular levels of Ki-67 and anti-apoptotic protein expression were compared between serum-starved ciRS-7-overexpressing cells and blank control groups. Ishikawa cell lines stably overexpressing both ciRS-7 and miR-7 were constructed, and Western blot was used to measure the levels of ER stress-related proteins and pro-apoptotic protein expression after ER stress induction. An Ishikawa cell line with stable ciRS-7 knockdown was established, and after ER stress induction in serum-starved cells, miR-7 levels were detected by qRT-PCR, while the expression levels of ER stress-related and pro-apoptotic proteins were assessed by Western blot. Results: Ishikawa cells overexpressing ciRS-7 exhibited significantly increased proliferative activity, migration, and invasion. Overexpression of ciRS-7 led to a significant decrease in miR-7 levels. Serum starvation for 24 hours successfully induced increased ER stress levels in Ishikawa cells. Intracellular miR-7 levels in ciRS-7-overexpressing Ishikawa cells were significantly lower than those in negative control cells, rendering them more resistant to ER stress and exhibiting significantly lower levels of pro-apoptotic proteins. Dual overexpression of ciRS-7 and miR-7 resulted in decreased resistance to starvation-induced ER stress and significantly higher expression levels of apoptotic proteins. Knockdown of ciRS-7 increased cellular miR-7 levels, diminished cell resistance to starvation-induced ER stress, and promoted apoptosis. Conclusion: CiRS-7 expression can promote EC cell proliferation, migration, and invasion, and enhance EC cell resistance to starvation-induced ER stress by inhibiting miR-7 expression.
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[1] Crosbie E J,Kitson S J,Mcalpine J N,et al.Endometrial cancer[J].Lancet,2022,399(10333):1412-1428.
[2] Terzic M,Aimagambetova G,Kunz J,et al.Molecular basis of endometriosis and endometrial cancer:current knowledge and future perspectives[J].Int Mol Sci,2021,22(17):9274.
[3] Marfn-Jinmenez J A,Garcfa-Mulero S,Matfas-Guiu X,et al.Facts and hopes in immunotherapy of endometrial cancer[J].Clin Cancer Res,2022,28(22):4849-4860.
[4] Kim W R,Park E G,Lee D H,et al.The tumorigenic role of circular RNA-microRNA axis in cancer[J].Int Mol Sci,2023,24(3):3050.
[5] Hansen T B,Wiklund E D,Bramsen J B,et al.miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA[J].EMBO,2011,30(21):4414-4422.
[6] Chen J,Yang J,Fei X,et al.CircRNA ciRS-7:a novel oncogene in multiple cancers[J].Int Biol Sci,2021,17(1):379-389.
[7] 吴龙云,李冰洁,曾长.子宫内膜癌患者组织中PD-L1、Ki-67表达及意义[J].河北医药,2024,46(11):1674-1677.
[8] Chen X,Shi C,He M,et al.Endoplasmic reticulum stress:molecular mechanism and therapeutic targets[J].Signal Transduct Target Ther,2023,8(1):352.
[9] Wan Y,Yang L,Jiang S,et al.Excessive apoptosis in ulcerative colitis:crosstalk between apoptosis,ROS,ER stress and intestinal homeostasis[J].Inflamm Bowel Dis,2022,28(4):639-648.
[10] Wang G S,Chen J Y,Chen W C,et al.Surfactin induces ER stress-mediated apoptosis via IRE1-ASK1-JNK signaling in human osteosarcoma[J].Environ Toxicol,2022,37(3):574-584.
[11] Zhou Q,Ye F,Qiu J,et al.Dihydroartemisinin induces ER stress-mediated apoptosis in human tongue squamous carcinoma by regulating ROS production[J].Anticancer Agents Med Chem,2022,22(16):2902-2908. |
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2025, Vol. 31 
