Open Access

miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer

  • Authors:
    • Yuqing Pei
    • Kexin Li
    • Xiaoying Lou
    • Yue Wu
    • Xin Dong
    • Wenpeng Wang
    • Ning Li
    • Donghong Zhang
    • Wei Cui
  • View Affiliations

  • Published online on: May 25, 2020     https://doi.org/10.3892/or.2020.7623
  • Pages: 438-448
  • Copyright: © Pei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent studies have revealed the oncogenic role of notch reporter 3 (NOTCH3) in ovarian cancer (OC). However, the possible regulators and mechanisms underlying notch receptor 3 (NOTCH3)‑mediated behaviors in OC remain to be completely investigated. In the present study, we aimed to identify regulators of NOTCH3 and their interactions underlying the pathogenesis of OC. Bioinformatics analysis and luciferase reporter assay were used to identify potential regulatory miRNAs and lncRNAs of NOTCH3 in OC. Several in vivo and in vitro assays were performed to evaluate their effects on the proliferative ability mediated by NOTCH3. We identified microRNA‑1299 (miR‑1299) as a novel negative regulator of NOTCH3. miR‑1299 was downregulated in OC and was found to be considerably correlated with tumor differentiation. Upregulation of miR‑1299 inhibited cell proliferation, colony formation, and 5‑ethynyl‑2'‑deoxyuridine (EdU) incorporation, as well as induced cell cycle arrest in the G0G1 phase in OC cells. Overexpression of miR‑1299 in xenograft mouse models suppressed tumor growth in vivo. The lncRNA taurine upregulated gene 1 (TUG1), acting as a sponge of miR‑1299, was found to upregulate NOTCH3 expression and promote cell proliferation in OC through the competing endogenous RNA mechanism. In addition, TUG1 was found to be a potential downstream target of NOTCH3, forming a miR‑1299/NOTCH3/TUG1 feedback loop in the development of OC. Collectively, our findings improve the understanding of NOTCH3‑mediated regulation in OC pathogenesis and facilitate the development of miRNA‑ and lncRNA‑directed diagnostics and therapeutics against this disease.

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August-2020
Volume 44 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Pei Y, Li K, Lou X, Wu Y, Dong X, Wang W, Li N, Zhang D and Cui W: miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer. Oncol Rep 44: 438-448, 2020
APA
Pei, Y., Li, K., Lou, X., Wu, Y., Dong, X., Wang, W. ... Cui, W. (2020). miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer. Oncology Reports, 44, 438-448. https://doi.org/10.3892/or.2020.7623
MLA
Pei, Y., Li, K., Lou, X., Wu, Y., Dong, X., Wang, W., Li, N., Zhang, D., Cui, W."miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer". Oncology Reports 44.2 (2020): 438-448.
Chicago
Pei, Y., Li, K., Lou, X., Wu, Y., Dong, X., Wang, W., Li, N., Zhang, D., Cui, W."miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer". Oncology Reports 44, no. 2 (2020): 438-448. https://doi.org/10.3892/or.2020.7623