Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Int J Oncol. 2019 May;54(5):1771-1784. doi: 10.3892/ijo.2019.4731. Epub 2019 Feb 27.
Ovarian cancer (OC) is the gynecological malignancy type with the highest mortality rate in females. The regulatory effect of microRNAs (miRs) on their target genes serves a key role in tumor development. Therefore, in the present study, whether miR let‑7d‑5p targeting high mobility group A1 (HMGA1) regulated biological characteristics and chemosensitivity of OC cells by mediating the p53 signaling pathway was investigated. The let‑7d‑5p level was detected in OC tissues and adjacent normal tissues, followed by detection in OC cell lines SKOV3, A2780, OVCAR‑3 and CaOV3, and human normal ovarian epithelial cell line (IOSE‑80), in order to select the OC cell line for the following experiments. Subsequently, OC cells were treated with the let‑7d‑5p mimic, siHMGA1 and Tenovin‑1. The targeting association between let‑7d‑5p and HMGA1 was then examined, and the OC cell viability, migration, cycle and apoptosis were evaluated. Subsequently, the chemosensitivity of OC cells to cisplatin was verified. Finally, expression levels of let‑7d‑5p, HMGA1, p21, B‑cell lymphoma‑2 (Bcl‑2)‑associated X (Bax), p27, p53 wild‑type (p53wt), p53 mutated (p53mut), proliferating cell nuclear antigen (PCNA), cyclin‑dependent kinase 2 (CDK2), matrix metallopeptidase (MMP)2, MMP9 and Bcl‑2 were determined. As demonstrated in the results, let‑7d‑5p expression was low in OC tissues and had an increased reduction in the OVCAR‑3 cell line. HMGA1 was confirmed as a target of let‑7d‑5p, and its expression was also silenced by let‑7d‑5p. let‑7d‑5p repressed OC cell viability, migration, cell cycle progression and apoptosis, while it promoted the chemosensitivity of OC cells to cisplatin by targeting HMGA1. The expression of let‑7d‑5p, p21, Bax, p27 and p53wt was increased, while that of HMGA1, p53mut, PCNA, CDK2, MMP2, MMP9 and Bcl‑2 was reduced following cell transfection. The results in the present study provided evidence that let‑7d‑5p may suppress proliferation, and facilitate apoptosis and cisplatin chemosensitivity of OC cells by silencing HMGA1 via the p53 signaling pathway.
卵巢癌(OC)是女性中死亡率最高的妇科恶性肿瘤。微小 RNA(miRs)对其靶基因的调节作用在肿瘤发展中起着关键作用。因此,本研究探讨了 miR let-7d-5p 靶向高迁移率族蛋白 A1(HMGA1)是否通过调节 p53 信号通路来调节 OC 细胞的生物学特性和化疗敏感性。检测 OC 组织和相邻正常组织中的 let-7d-5p 水平,然后检测 OC 细胞系 SKOV3、A2780、OVCAR-3 和 CaOV3 以及人正常卵巢上皮细胞系(IOSE-80),以选择用于以下实验的 OC 细胞系。随后,用 let-7d-5p 模拟物、siHMGA1 和 Tenovin-1 处理 OC 细胞。然后检测 let-7d-5p 与 HMGA1 的靶向关联,并评估 OC 细胞的活力、迁移、周期和凋亡。随后,验证 OC 细胞对顺铂的化疗敏感性。最后,测定 let-7d-5p、HMGA1、p21、B 细胞淋巴瘤-2(Bcl-2)相关 X(Bax)、p27、p53 野生型(p53wt)、p53 突变型(p53mut)、增殖细胞核抗原(PCNA)、细胞周期蛋白依赖性激酶 2(CDK2)、基质金属蛋白酶 2(MMP2)、基质金属蛋白酶 9(MMP9)和 Bcl-2 的表达水平。结果表明,OC 组织中 let-7d-5p 表达降低,OVCAR-3 细胞系中表达降低更为明显。HMGA1 被确认为 let-7d-5p 的靶基因,其表达也被 let-7d-5p 沉默。let-7d-5p 抑制 OC 细胞活力、迁移、细胞周期进程和凋亡,同时通过靶向 HMGA1 促进 OC 细胞对顺铂的化疗敏感性。转染细胞后 let-7d-5p、p21、Bax、p27 和 p53wt 的表达增加,而 HMGA1、p53mut、PCNA、CDK2、MMP2、MMP9 和 Bcl-2 的表达减少。本研究结果表明,let-7d-5p 可能通过 p53 信号通路沉默 HMGA1 抑制 OC 细胞增殖,并促进细胞凋亡和顺铂化疗敏感性。