OncoTargets and Therapy (Feb 2021)

Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3

  • Zhu J,
  • Han S

Journal volume & issue
Vol. Volume 14
pp. 1331 – 1340

Abstract

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Jinming Zhu,1 Shichao Han2 1Department of Oncology, Affiliated Zhongshan Hospital, Dalian University, Dalian, Liaoning, 116000, People’s Republic of China; 2Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116021, People’s Republic of ChinaCorrespondence: Shichao HanDepartment of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116021, People’s Republic of ChinaEmail [email protected]: Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was reported to be dysregulated in several cancer types; however, the role of DARS-AS1 in cervical cancer remains unclear.Methods: Flow cytometry and transwell invasion assays were performed to determine the apoptosis and invasion in cervical cancer cells. In addition, RNA pull-down and fluorescence in situ hybridization (FISH) assays were conducted to assess the interaction between DARS-AS1 and IGF2BP3 in cervical cancer cells.Results: Downregulation of DARS-AS1 significantly induced apoptosis and cell cycle arrest in cervical cancer cells. Meanwhile, the invasion ability of cervical cancer cells was inhibited by DARS-AS1 knockdown as well. RNA pull-down and FISH results showed that DARS-AS1 interacted with IGF2BP3. Mechanistically, DARS-AS1 positively regulated IGF2BP3 expression via stabilization of IGF2BP3 mRNA. Rescue assays confirmed that DARS-AS1 regulated the progression of cervical cancer through interacting with IGF2BP3 in vitro. In addition, in vivo experiments revealed that downregulation of DARS-AS1 inhibited tumor growth in SiHa xenograft model.Conclusion: In this study, we found that downregulation of DARS-AS1 could inhibit the growth of cervical cancer cells via inhibition of IGF2BP3, suggesting DARS-AS1 might serve as a potential target for the treatment of cervical cancer.Keywords: cervical cancer, lncRNAs, DARS-AS1, IGF2BP3, apoptosis

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