LncRNA-LALR1 upregulates small nucleolar RNA SNORD72 to promote growth and invasion of hepatocellular carcinoma

Aging (Albany NY). 2020 Mar 11;12(5):4527-4546. doi: 10.18632/aging.102907. Epub 2020 Mar 11.

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and currently the second leading cause of cancer-related mortality worldwide. One recent study reported that lncRNA-LALR1 promotes liver regeneration, the role and underlying mechanisms of lncRNA-LALR1 in HCC remain largely unknown. In this study, we demonstrated that lncRNA-LALR1 was significantly upregulated in HCC tissues compared with adjacent tissues and high expression of lncRNA-LALR1 was associated with advanced TNM stage, poor differentiation, and distant metastasis. RNA Fluorescence in situ hybridization analysis showed lncRNA-LALR1 was expressed not only in cytoplasm but also in nucleolus. Knockdown of lncRNA-LALR1 obviously inhibited HCC cells growth and invasion in vivo and in vitro. Besides, transcriptomic analysis and subsequent confirmation revealed that lncRNA-LALR1 upregulated small nucleolar RNA SNORD72 via binding with SNORD72 and stabilized ID2 mRNA. SNORD72 was overexpressed in HCC tissues and enhanced HCC cells proliferation, colony formation and invasion. Overexpression of SNORD72 could also stabilize ID2 mRNA and rescue the inhibitory effect of silencing lncRNA-LALR1. In conclusion, lncRNA-LALR1 is highly expressed in HCC and promotes tumor growth and invasion by upregulating SNORD72 to stabilize ID2 mRNA, implying that lncRNA-LALR1 might be a novel target for intervention of HCC.

Keywords: HCC; ID2; SNORD72; lncRNA-LALR1; mRNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • RNA, Long Noncoding*
  • RNA, Small Nucleolar*
  • Up-Regulation*

Substances

  • RNA, Long Noncoding
  • RNA, Small Nucleolar