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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