Regulatory Effect of miR497-5p–CCNE1 Axis in Triple-Negative Breast Cancer Cells and Its Predictive Value for Early Diagnosis
Authors Liu WW, Li WD, Zhang YJ, Zhang ML
Received 28 September 2020
Accepted for publication 5 November 2020
Published 18 January 2021 Volume 2021:13 Pages 439—447
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Eileen O'Reilly
Wei-Wei Liu, Wei-Dong Li, Yan-Ju Zhang, Man-Li Zhang
Breast Center, Cangzhou People’s Hospital, Cangzhou 061000, Hebei Province, People’s Republic of China
Correspondence: Man-Li Zhang
Breast Center, Cangzhou People’s Hospital, Intersection of Chongqing Road and Jilin North Road, Yunhe District, Cangzhou 061000, Hebei Province, People’s Republic of China
Objective: To explore the regulatory role of miR497-5p–CCNE1 axis in triple-negative breast cancer (TNBC) cells and its predictive value for early diagnosis.
Methods: Cancer tissue and adjacent tissue samples were collected from 86 patients with TNBC.RT-PCR was used to detect the expression of miR497-5p and CCNE1 (target gene) mRNA, determined by biological prediction in tissue and TNBC cells. ROC was used to analyze the diagnostic value of miR497-5p in TNBC. MTT, invasion, and flow cytometry were used to detect the proliferation, invasion, cycle, apoptosis rate, and expression of related proteins of TNBC cells with overexpression of miR497-5p or knockdown of CCNE1.
Results: RT-qPCR results showed that miR497-5p levels were significantly downregulated in TNBC tissue and cells, while CCNE1 expression was significantly upregulated, and miR497-5p expression was negatively correlated with that of CCNE1 (P< 0.001). ROC analysis showed that the AUC of miR497-5p for TNBC was > 0.9, which had better diagnostic value. The cell tests revealed that miR497-5p played a role in tumor inhibition, including inhibiting proliferation and invasion of TNBC cells, blocking the cell cycle, and promoting apoptosis. Bioinformatic prediction and subsequent experiments revealed that CCNE1 was the direct target of miR497-5p. Furthermore, after knocking down the expression of CCNE1 in TNBC cells, the proliferation and invasion of TNBC cells were significantly inhibited, the cell cycle blocked, and the apoptosis rate significantly increased (P< 0.001), and expression of the proapoptosis-related proteins Bax and caspase 3 (cleaved) were upregulated, while expression of the antiapoptosis-related protein BCL2 was downregulated (P< 0.001).
Conclusion: miR497-5p inhibited the proliferation and invasion of TNBC cells by targeting CCNE1, blocked the cell cycle and promoted the apoptosis of TNBC cells, and had better diagnostic value for TNBC. miR497-5p can be used as a new potential target for the treatment of TNBC.
Keywords: miR497-5p, TNBC, CCNE1, proliferation, invasion, apoptosis
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