lncRNA HAND2-AS1 Inhibits Liver Cancer Cell Proliferation and Migration by Upregulating SOCS5 to Inactivate the JAK-STAT Pathway

Cancer Biother Radiopharm. 2020 Mar;35(2):143-152. doi: 10.1089/cbr.2019.2958.

Abstract

Objective: lncRNA HAND2 antisense RNA 1 (HAND2-AS1) is consistently well recognized to suppress multiple tumors, while its function was uncertified in liver cancer. Materials and Methods: qRT-PCR analysis and TCGA database discovered the expression in liver cancer. CCK-8 and Transwell migration assay demonstrated the impact of HAND2-AS1 on cell proliferation and migration. Bioinformatic analysis and luciferase reporter assay were utilized to monitor the binding between HAND2-AS1 or SOCS5 mRNA and miR-3118. The function of SOCS5 on inactivating the JAK-STAT pathway was confirmed through Western blot assays. Rescue experiments unmasked that HAND2-AS1-mediated SOCS5 affected cell proliferation and migration through the JAK-STAT pathway in liver cancer. Results: The authors discovered the downregulated HAND2-AS1 in liver cancer cells. HAND2-AS1 augmentation apparently impaired the capacity of liver cancer viability, proliferation, and migration. Cytoplasmic HAND2-AS1 directly bound to miR-3118 and released SOCS5, leading to upregulation of SOCS5. Next, the negative regulator role of SOCS5 in the adjusting JAK-STAT pathway was reconfirmed in this study. Conclusions: HAND2-AS1 enhanced inactivation of the JAK-STAT pathway through sponging miR-3118 and facilitating SOCS5 to retard cell proliferation and migration in liver cancer.

Keywords: HAND2-AS1; JAK-STAT pathway; SOCS5; liver cancer; miR-3118.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Hep G2 Cells
  • Humans
  • Janus Kinases / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Transfection
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • SOCS5 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling Proteins
  • long non-coding RNA HAND2-AS1, human
  • Janus Kinases