Role of lncRNA LINC01194 in hepatocellular carcinoma via the miR-655-3p/SMAD family member 5 axis

Bioengineered. 2022 Jan;13(1):1115-1125. doi: 10.1080/21655979.2021.2017678.

Abstract

Long non-coding RNAs (lncRNAs) are involved in developing hepatocellular carcinoma (HCC). The present study explored the role of lncRNA LINC01194, which is upregulated in HCC tissues and might be a vital regulator in HCC progression. Levels of LINC01194, microRNA (miR)-655-3p, and SMAD family member 5 (SMAD5) were assessed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The bioactivity of Huh-7 cells was assessed using cell counting kit-8 and transwell assays and flow cytometry. Western blotting was conducted to measure the expression of invasion- and apoptosis-related proteins. The relationships between lncRNA LINC01194 and miR-655-3p, and miR-655-3p and SMAD5 were predicted using StarBase and TargetScan, and further verified using a dual-luciferase reporter assay. LINC01194 was overexpressed in HCC cells and in clinical samples. ILINC01194 silencing suppressed proliferation and migration; however, it promoted apoptosis in HCC cell lines. We also confirmed that miR-655-3p could bind to LINC01194, and miR-655-3p was downregulated in HCC. The upregulation of miR-655-3p suppressed HCC cell invasion and migration, and enhanced the number of apoptotic cells. SMAD5, which was overexpressed in HCC cell lines, was directly targeted by miR-655-3p. Therefore, LINC01194 promoted HCC development by decreasing miR-655-3p expression and may serve as a promising therapeutic target for HCC patients.

Keywords: Long non-coding RNA; SMAD family member 5; hepatocellular carcinoma; long intergenic non-protein coding RNA 1194; microRNA-655-3p.

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics*
  • Smad5 Protein / genetics*
  • Up-Regulation

Substances

  • MIRN655 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SMAD5 protein, human
  • Smad5 Protein

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.