LncRNA CDKN2B-AS1 promotes the progression of ovarian cancer by miR-143-3p/SMAD3 axis and predicts a poor prognosis

Neoplasma. 2020 Jul;67(4):782-793. doi: 10.4149/neo_2020_190617N515. Epub 2020 Apr 16.

Abstract

Long noncoding RNAs (LncRNAs) show great potential as the therapeutic targets attributing to their implication in the progression of various human cancers, including ovarian cancer (OC). Here, we aimed to explore the biological function of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in OC and its mechanism of action. The abundances of CDKN2B-AS1, miR-143-3p, and SMAD3 mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8) was performed to analyze cell proliferation. Cell apoptosis was assessed by flow cytometry and western blot analyses. Transwell assay was utilized to analyze cell migration and invasion abilities. Tumor xenograft was performed to confirm the role of CDKN2B-AS1 in ovarian tumor growth in vivo. The protein level of SMAD3 was examined by western blot assay. The interaction between CDKN2B-AS1 and miR-143-3p, or miR-143-3p and SMAD3 was demonstrated by bioinformatic, luciferase reporter, qRT-PCR and western blot analyses. CDKN2B-AS1 was upregulated in OC and correlated with clinicopathologic features. The knockdown of CDKN2B-AS1 hampered the development of OC, as reflected by the suppression of cell proliferation, migration, and invasion, and the enhancement of cell apoptosis, whereas the effects could be rescued by the overexpression of SMAD3. The absence of CDKN2B-AS1 blocked tumor growth in vivo. CDKN2B-AS1 served as a molecular sponge for miR-143-3p, leading to the derepression of miR-143-3p target SMAD3, which eventually triggered the progression of OC. In conclusion, CDKN2B-AS1 promoted tumor growth, invasion, and migration of OC by regulation of miR-143-3p/SMAD3 axis, hinting that CDKN2B-AS1 might be a potential biomarker for OC diagnosis and treatment.

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p15
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / genetics
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / physiology
  • Smad3 Protein* / genetics

Substances

  • CDKN2B antisense RNA, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • MIRN143 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SMAD3 protein, human
  • Smad3 Protein