Circular RNA hsa_circ_0026344 suppresses gastric cancer cell proliferation, migration and invasion via the miR-590-5p/PDCD4 axis

J Pharm Pharmacol. 2022 Aug 19;74(8):1193-1204. doi: 10.1093/jpp/rgac032.

Abstract

Objectives: Circular RNA (CircRNA) is a class of non-coding RNA transcripts, with multiple pathophysiological functions. Instead, the mechanism and function of circRNA in gastric cancer (GC) are not fully deciphered.

Methods: CircRNA_0026344 (circ_0026344), microRNA (miR)-590-5p and programmed cell death 4 (PDCD4) mRNA expression levels in GC tissues and cells were probed by quantitative real-time PCR. Cell viability, migration and aggressiveness were examined by cell counting kit-8 and transwell assays. Additionally, the interplay among circ_0026344, miR-590-5p and PDCD4 was verified with bioinformatics and dual-luciferase reporter gene assay. Western blot was conducted to probe PDCD4 protein expression.

Key findings: Circ_0026344 expression was underexpressed in GC tissues and cells, which was associated with clinicopathological characteristics such as tumour size, tumor-node-metastasis stage and lymph node metastasis. Circ_0026344 overexpression restrained the malignant biological behaviours of GC cells, while circ_0026344 knockdown functioned oppositely. Circ_0026344 could act as a competing endogenous RNA of miR-590-5p to negatively modulate its expression, and this miRNA could mitigate the impact of circ_0026344 on GC cells. In addition, PDCD4 was identified as the downstream target of miR-590-5p, and PDCD4 expression was positively modulated by circ_0026344.

Conclusions: Circ_0026344 up-regulates PDCD4 expression via sponging miR-590-5p, thus inhibiting the progression of GC. This study further expounds the underlying molecular mechanism in the GC progression.

Keywords: PDCD4; cell viability and metastasis; circ_0026344; gastric cancer; miR-590-5p.

MeSH terms

  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • RNA-Binding Proteins* / genetics
  • Stomach Neoplasms* / pathology

Substances

  • Apoptosis Regulatory Proteins
  • MIRN590 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Circular
  • RNA-Binding Proteins