LncRNA TMPO-AS1 Aggravates the Development of Hepatocellular Carcinoma via miR-429/GOT1 Axis

Am J Med Sci. 2020 Dec;360(6):711-720. doi: 10.1016/j.amjms.2020.08.010. Epub 2020 Aug 10.

Abstract

Background: Hepatocellular carcinoma (HCC), featuring uncontrolled proliferation and migration of tumor cells, is one of the most serious malignancies with high morality. An increasing number of evidences have demonstrated that long noncoding RNAs (lncRNAs) are involved in the progression of multiple cancers. It has been acknowledged that lncRNA TMPO-AS1 plays an oncogenic role in diverse cancers.

Methods: Reverse transcription‑quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of TMPO-AS1, miR-429 and GOT1 in HCC tissues and cell lines. Cell viability, proliferation, apoptosis, and stemness characteristics were detected by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, sphere formation and western blot assays, separately. The relationship among TMPO-AS1, miR-429 and GOT1 was predicted by starBase database and confirmed using luciferase reporter and RNA pull-down assays.

Results: In this study, our findings revealed that TMPO-AS1 expression was upregulated in HCC tissues and cell lines. TMPO-AS1 aggravated HCC progression via promoting cell proliferation, stemness as well as suppressing cell apoptosis. Further, molecular mechanism exploration discovered that TMPO-AS1 functioned as a molecular sponge for miR-429 and GOT1 served as a downstream target gene of miR-429 in HCC. Furthermore, there was a negative relationship between GOT1 and miR-429 as well as a positive correlation between GOT1 and TMPO-AS1 in HCC. Rescue assays suggested that overexpression of GOT1 partially reversed the inhibitory effects of TMPO-AS1 knockdown on HCC progression.

Conclusions: Taken together, these findings indicated that TMPO-AS1 acted as a tumor motivator to expedite HCC progression via targeting miR-429/GOT1 axis, which may provide a fresh treatment strategy for HCC.

Keywords: GOT1; Hepatocellular carcinoma; TMPO-AS1; miR-429.

MeSH terms

  • Aspartate Aminotransferase, Cytoplasmic / metabolism*
  • Carcinoma, Hepatocellular / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • MicroRNAs / metabolism*
  • Nuclear Proteins / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Thymopoietins / metabolism*

Substances

  • MIRN429 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Thymopoietins
  • TMPO protein, human
  • Aspartate Aminotransferase, Cytoplasmic
  • GOT1 protein, human