LncRNA OGFRP1 promotes cell proliferation and suppresses cell radiosensitivity in gastric cancer by targeting the miR-149-5p/MAP3K3 axis

J Mol Histol. 2022 Apr;53(2):257-271. doi: 10.1007/s10735-022-10058-w. Epub 2022 Jan 20.

Abstract

Gastric cancer (GC) is an aggressive malignancy with high incidence and mortality. Radiotherapy is a common treatment for patients with advanced GC. Many long noncoding RNAs (lncRNAs) have been verified to affect the radiosensitivity of multiple cancers in previous studies. Nevertheless, whether lncRNA opioid growth factor receptor pseudogene 1 (OGFRP1) affects the radiosensitivity of GC has not been determined. We hypothesized that OGFRP1 might affect cellular processes in GC development. The present study aims to explore the role of OGFRP1 in GC development. First, high expression of OGFRP1 in GC tissues and cells was determined through RT-qPCR. Subsequently, functional assays including colony formation assays, 5-Ethynyl-2'-deoxyuridine assays and flow cytometry analyses were performed to probe the biological functions of OGFRP1 in GC. Specifically, the effect of OGFRP1 on the radiosensitivity of GC cells was detected. Subsequently, with the help of the starBase tool, we found that miR-149-5p might bind to OGFRP1, which was confirmed through a luciferase reporter assay. Furthermore, we identified that MAP3K3 was targeted by miR-149-5p in GC cells. Finally, the results from rescue experiments validated that enhanced MAP3K3 expression counteracted the effect of OGFRP1 silencing on GC cell proliferation, apoptosis and radiosensitivity. Overall, OGFRP1 was determined to promote GC cell proliferation while suppressing cell apoptosis and radiosensitivity by regulating the miR-149-5p/MAP3K3 axis.

Keywords: Gastric cancer; MAP3K3; Radiosensitivity; lncRNA OGFRP1; miR-149-5p.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • MAP Kinase Kinase Kinase 3
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Radiation Tolerance / genetics
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / radiotherapy

Substances

  • MIRN149 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • MAP Kinase Kinase Kinase 3
  • MAP3K3 protein, human