Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3
Authors Zhu J, Han S
Received 16 September 2020
Accepted for publication 16 January 2021
Published 25 February 2021 Volume 2021:14 Pages 1331—1340
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Sanjay Singh
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 China
Correspondence: Shichao Han
Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116021, People’s Republic of China
Email [email protected]
Background: 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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