Cancer Management and Research (2021-05-01)

LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer

  • Jiang X,
  • Cheng Y,
  • He Y,
  • Cong S,
  • Sun L,
  • Wu D,
  • Wu H,
  • Zhang G

Journal volume & issue
Vol. Volume 13
pp. 3817 – 3826

Abstract

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Xinyan Jiang, Yan Cheng, Yanan He, Shanshan Cong, Liyuan Sun, Di Wu, Han Wu, Guangmei Zhang The First Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Guangmei Zhang Building 2, 23 Youzheng Road, Harbin, 150001, People’s Republic of ChinaEmail [email protected]: Ovarian cancer has one of the highest mortality rates among all gynaecological malignancies, and increasing evidence suggests that lncRNAs are widely involved in the development of ovarian tumours. This study aimed to investigate the mechanism of the LNC00115/miR-7/ERK axis in the cisplatin resistance of ovarian cancer cells.Methods: The expression of miR-7 and LNC00115 in ovarian cancer cell lines and tissues was detected by qRT-PCR. The ovarian cancer cell lines were constructed by overexpressing or knocking down the expression of LNC00115 or miR-7. CCK-8, transwell invasion, Western blot, immunohistochemistry, and luciferase reporter assays were carried out to identify the targets of LNC00115 and explore its roles and mechanisms in ovarian cancer. A nude mouse model was established, and the expression of LNC00115, miR-7 and ERK was detected. The changes in the tumours and body weights of the nude mice were measured.Results: LNC00115 was upregulated in ovarian cancer tissues and cisplatin-resistant ovarian cancer cells. Moreover, LNC00115 promoted the cisplatin resistance, invasion and migration of ovarian cancer cells. LNC00115 was shown to directly target miR-7, and miR-7 was downregulated in ovarian cancer tissues and cisplatin-resistant ovarian cancer cells. miR-7 inhibited the cisplatin resistance, invasion and migration of ovarian cancer cells and directly targeted ERK. ERK was overexpressed in cisplatin-resistant ovarian cancer cells and ovarian cancer tissues. In animal experiments, overexpression of LNC00115 enhanced the cisplatin resistance of ovarian cancer cells, while miR-7 had the opposite effect. Mechanistically, LNC00115 sponged miR-7 to increase the expression of ERK, which in turn enhanced the cisplatin resistance of ovarian cancer.Conclusion: Our data clarify the mechanism by which the LNC00115/miR-7/ERK axis promotes cisplatin resistance and provide a new clinical strategy for combating cisplatin resistance in ovarian cancer.Keywords: cisplatin resistance, miR-7, LNC00115, ovarian cancer, ERK

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