Long non-coding RNA MSC-AS1 facilitates the proliferation and glycolysis of gastric cancer cells by regulating PFKFB3 expression

Int J Med Sci. 2021 Jan 1;18(2):546-554. doi: 10.7150/ijms.51947. eCollection 2021.

Abstract

Long non-coding RNA musculin antisense RNA 1 (lncRNA MSC-AS1) has been recognized as an oncogene in pancreatic cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and renal cell carcinoma. However, the functional significance of MSC-AS1 and its underlying mechanism in gastric cancer (GC) progression remain unclear. In this study, we demonstrated that the expression of MSC-AS1 in GC tissues was significantly higher than that in non-tumor tissues. Moreover, the elevated level of MSC-AS1 was detected in GC cells (MKN-45, AGS, SGC-7901, and MGC-803) compared to normal GES-1 gastric mucosal cells. The cancer genome atlas (TCGA) data further indicated that the high level of MSC-AS1 was closely correlated with advanced tumor stage and poor prognosis of GC. Next, we revealed that MSC-AS1 knockdown inhibited the proliferation, glucose consumption, lactate production, and pyruvate production of MGC-803 cells. Conversely, MSC-AS1 overexpression enhanced the proliferation and glycolysis of AGC cells. Mechanistically, modulating MSC-AS1 level affected the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), but did not impact the levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) in GC cells. Based on this, we reversed the MSC-AS1 knockdown-induced the inhibition of cell proliferation and glycolysis by restoring PFKFB3 expression in MGC-803 cells. In conclusion, MSC-AS1 facilitated the proliferation and glycolysis of GC cells by maintaining PFKFB3 expression.

Keywords: Gastric cancer; Glycolysis; LncRNA; MSC-AS1; PFKFB3; Proliferation.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Female
  • Gastrectomy
  • Gastric Mucosa / pathology
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Phosphofructokinase-2 / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Warburg Effect, Oncologic*

Substances

  • RNA, Long Noncoding
  • PFKFB3 protein, human
  • Phosphofructokinase-2