LncRNA LINC00460 takes a stimulating role on hepatocellular carcinoma stemness property

Cell Cycle. 2021 Oct;20(20):2102-2113. doi: 10.1080/15384101.2021.1940627. Epub 2021 Oct 6.

Abstract

Abundant researches have stated that long noncoding RNAs (lncRNAs) are crucial molecules in intricate progression of various cancers in terms of their influence on cell stemness. However, no research has discussed the role of LINC00460 in the stemness of hepatocellular carcinoma (HCC). RT-qPCR and western blot were utilized to respectively examine the RNA and protein levels. Aldehyde dehydrogenase 1 (ALDH1) assays and sphere formation assay were performed to detect cell stemness property in vitro and in vivo subcutaneous xenograft tumor assay was performed to detect tumor growth. Interaction between RNAs was explored by luciferase reporter assays and RNA pull-down assays. Our results showed that LINC00460 was markedly over-expressed in HCC and silencing LINC00460 impaired cell stemness. Additionally, LINC00460 knockdown curbed proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) and drove apoptosis of HCC cells. Further, LINC00460 bound to miR-503-5p and miR-654-3p to protect t-complex 1 (TCP1) from being inhibited by miR-503-5p/miR-654-3p. Rescue experiments confirmed the effect of LINC00460/miR-503-5p/miR-654-3p/TCP1 on HCC cell stemness. In conclusion, LINC00460 aggravated cell stemness in HCC via targeting miR-503-5p/miR-654-3p and TCP1, suggesting that LINC00460 may work as a potential signature for cell stemness in HCC.[Figure: see text].

Keywords: LINC00460; TCP1; hepatocellular carcinoma; miR-503-5p; miR-654-3p; stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

The work was supported by the Natural Science Foundation of Hubei Province (2016CFC732).