circ_0044516 functions in the progression of gastric cancer by modulating MicroRNA-149-5p/HuR axis

Mol Cell Biochem. 2022 Sep;477(9):2161-2171. doi: 10.1007/s11010-020-04026-9. Epub 2021 Jan 8.

Abstract

Circular RNAs (circRNAs) have emerged as a multifunctional class of RNAs, while there is limited knowledge on their functions in the development of cancers. Herein, we performed the current study to probe into the regulatory mechanism of circ_0044516 in malignant behaviors of gastric cancer (GC) cells with the involvement of microRNA (miR)-149-5p/human antigen R (HuR) axis. Firstly, the expression levels of circ_0044516 in GC cell lines and normal gastric mucosal epithelial cells were determined by qRT-PCR, and GC cell lines with the highest expression of circ_0044516 were screened for further cell experiments. Subsequently, the biological functions of silenced circ_0044516 in GC were identified by CCK-8, colony formation, and transwell assays. Xenograft mouse models were established for in vivo verification. Furthermore, luciferase reporter, RIP, RNA pull-down assay and rescue experiments were performed to explore the sponge regulatory mechanism of circ_0044516. circ_0044516 was suggested to be highly expressed in GC cell lines, and circ_0044516 could promote GC cell proliferation, migration and invasion, as well as in vivo tumor growth. In addition, silenced circ-0044516 reversed the promotive roles in cell viability caused by overexpressed HuR. Furthermore, circ_0044516 mainly localized in the cytoplasm, which may act as a miR-149-5p sponge to modulate HuR expression, thereby playing an essential role in GC development. This study suggests that circ_0044516 may promote HuR expression through sponging miR-149-5p, thereby playing a part in GC progression.

Keywords: Gastric cancer; HuR; Invasion; Malignant behaviors; MicroRNA-149; Migration; Proliferation; circ_0044516.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Stomach Neoplasms* / metabolism

Substances

  • MIRN149 microRNA, human
  • MicroRNAs