Long non-coding RNA BLACAT2/miR-378a-3p/YY1 feedback loop promotes the proliferation, migration and invasion of uterine corpus endometrial carcinoma

被引:4
作者
Zhang, Chen [1 ]
Wang, Ruicong [2 ]
Li, Mengyuan [1 ]
Yang, Qing [1 ,3 ]
机构
[1] China Med Univ, Dept Obstet & Gynecol, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China
[2] Dalian Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, Dalian, Liaoning, Peoples R China
[3] China Med Univ, Dept Obstet & Gynecol, Shengjing Hosp, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China
关键词
uterine corpus endometrial carcinoma; lncRNA-BLACAT2; miR-378a-3p; YY1; cell behavior; CELL-PROLIFERATION; GENE-EXPRESSION; GASTRIC-CANCER; SURVIVAL; YY1;
D O I
10.3892/or.2023.8544
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Uterine corpus endometrial carcinoma (UCEC) is a common gynecological malignancy with high rates of mortality and morbidity. The expression of long non-coding RNA bladder cancer-associated transcript 2 (BLACAT2) has been previously found to be aberrantly upregulated in UCEC. However, the regulatory consequences of this in UCEC progression remain poorly understood. In the present study, human UCEC cell lines AN3CA and HEC-1-A were infected with lentiviruses to overexpress BLACAT2 (Lv-BLACAT2) or knock down BLACAT2 using short hairpin RNA (Lv-shBLACAT2). BLACAT2 overexpression was found to promote the G(1)/S transition of cell cycle progression and UCEC cell proliferation. In addition, BLACAT2 overexpression was observed to facilitate UCEC cell migration and invasion. By contrast, BLACAT2 knockdown resulted in inhibitory effects in UCEC cell physiology. BLACAT2 overexpression also contributed to the activation of the MEK/ERK pathway. Subsequently, BLACAT2 was demonstrated to bind to microRNA (miR)-378a-3p according to dual-luciferase assays, where it appeared to function as a sponge of miR-378a-3p in 293T cells. miR-378a-3p overexpression was found to suppress UCEC cell proliferation, invasion, and ERK activation. Lentivirus-mediated knockdown of its target, the transcription factor Yin Yang-1 (YY1), was observed to reverse the oncogenic effects of BLACAT2 overexpression. Furthermore, YY1 was found to bind to the promoter of BLACAT2, suggesting that YY1 can regulate BLACAT2 expression. To conclude, results from the present study suggest that BLACAT2, miR-378a-3p and YY1 can form a feedback loop instead of an unidirectional axis, which can in turn regulate UCEC tumorigenesis through the MEK/ERK pathway. The present study furthered the understanding of UCEC tumorigenesis and may provide novel therapeutic targets for UCEC treatment.
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页数:16
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