Identification of a new GLDC gene alternative splicing variant and its protumorigenic roles in lung cancer

Future Oncol. 2019 Dec;15(36):4127-4139. doi: 10.2217/fon-2019-0403. Epub 2019 Nov 27.

Abstract

Aim: To clarify the regulatory roles of GLDCV1, the first identified truncated glycine decarboxylase (GLDC), on cancer stem cells and tumorigenesis. Materials & methods: RT-PCR or RT-qPCR, immunoblotting and immunohistochemical staining were applied to assess gene expression. MTT, BrdU incorporation and colony formation assays were used to examine cell proliferation capacity. Soft agar colony formation and in vivo transplantation were applied to evaluate cellular transformation and tumorigenesis. Results & conclusion: Expression of GLDCV1 or GLDC was enhanced in non-small-cell lung cancer cell line and clinical samples. GLDCV1 overexpression induced MRC5 cell proliferation, transformation and tumorigenesis. Additionally, GLDCV1 increased lactate production and cancer stem cell marker expression and activated ERK and P38 pathways. Our study gained deeper insight into GLDC oncogene.

Keywords: alternative splicing variant; cancer stem cells; glycine decarboxylase; lung cancer; tumourigenesis.

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glycine Dehydrogenase (Decarboxylating) / genetics*
  • Glycine Dehydrogenase (Decarboxylating) / metabolism
  • Humans
  • Lactic Acid / metabolism
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System
  • Mice

Substances

  • Cell Cycle Proteins
  • Lactic Acid
  • Glycine Dehydrogenase (Decarboxylating)