LncRNA SAMD12-AS1 Promotes the Progression of Gastric Cancer via DNMT1/p53 Axis

Arch Med Res. 2021 Oct;52(7):683-691. doi: 10.1016/j.arcmed.2021.04.004. Epub 2021 May 4.

Abstract

Background: Long noncoding RNAs (lncRNAs) are essential modulators of cancers initiation and progression via regulating gene expression and biological behaviors. LncRNA SAMD12-AS1 has been validated to promote the progression of several cancers, while its role in gastric cancer (GC) remains unclear. This study aims to explore the role of LncRNA SAMD12-AS1 in GC.

Methods: qRT-PCR was performed to analyze the expression of lncRNA SAMD12-AS1 in GC tissues and cell lines, with Kaplan-Meier curve analyzing the correlation between LncRNA SAMD12-AS1 and prognosis. CCK-8 assay, and flow cytometry were applied to detect GC cells proliferation, cell cycle. Binding of RNA and proteins were detected via RNA binding protein immunoprecipitation (RIP) assay. Protein levels of oncogenesis-related genes were determined via western blotting.

Results: SAMD12-AS1 was highly up-regulated in human gastric cancer tissues and cell lines compared to their normal counterparts. High SAMD12-AS1 expression was closely related to TNM stage, and shorter survival span of patients with GC. Moreover, SAMD12-AS1 was also found to promote the oncogenic role of GC cells via inhibiting the P53 signaling pathway. Mechanistically, SAMD12-AS1 might performed its biological roles in GC via directly interacting with DNMT1 and facilitating DNMT1 repress the P53 signaling pathway.

Conclusion: Our study demonstrated that SAMD12-AS1 promoted GC progression via DNMT1/P53 axis, indicating SAMD12-AS1 may be envisioned as a novel biomarker of, and therapeutic target for GC.

Keywords: Biomarker; DNMT1; Gastric cancer; LncRNA SAMD12-AS1; P53.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • RNA, Long Noncoding* / genetics
  • Stomach Neoplasms* / genetics
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human