MicroRNA let‑7d‑5p rescues ovarian cancer cell apoptosis and restores chemosensitivity by regulating the p53 signaling pathway via HMGA1

Chen,Yan‑Nan; Ren,Chen‑Chen; Yang,Li; Nai,Man‑Man; Xu,Yi‑Ming; Zhang,Feng; Liu,Yan

doi:10.3892/ijo.2019.4731

MicroRNA let‑7d‑5p rescues ovarian cancer cell apoptosis and restores chemosensitivity by regulating the p53 signaling pathway via HMGA1

Authors:
- Yan‑Nan Chen
- Chen‑Chen Ren
- Li Yang
- Man‑Man Nai
- Yi‑Ming Xu
- Feng Zhang
- Yan Liu
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Affiliations: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: February 27, 2019 https://doi.org/10.3892/ijo.2019.4731
Pages: 1771-1784

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Abstract

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.

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