Research Paper Volume 12, Issue 5 pp 4527—4546

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

Lin-Hong Mao 1, , Si-Yuan Chen 1, , Xiao-Qin Li 1, , Feng Xu 1, , Jing Lei 1, , Qing-Liang Wang 2, , Li-Yang Luo 1, , Hai-Yan Cao 1, , Xin Ge 1, , Tao Ran 1, , Xue Li 1, , Min Zou 1, , Zhi-Hang Zhou 1, *, , Xiao-Ling Wu 1, *, , Song He 1, *, ,

  • 1 Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2 Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
* Equal contribution

received: November 19, 2019 ; accepted: February 5, 2020 ; published: March 11, 2020 ;

https://doi.org/10.18632/aging.102907
How to Cite

Copyright © 2020 Mao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

ActD: actinomycin D; bHLH: basic helix-loop-helix; CCK-8: cell Counting Kit-8; EMT: epithelial-mesenchymal transition; FISH: fluorescence in situ hybridization; HCC: hepatocellular carcinoma; H1FX: histone 1FX; ID: inhibitors of DNA binding and cell differentiation; LncRNAs: long non-coding RNAs; PRC2: polycomb repressive complex 2. RNA-Seq: RNA Sequencing; SNORDs: C/D box snoRNAs; SNORAs: H/ACA box snoRNAs.