miR-615-5p prevents proliferation and migration through negatively regulating serine hydromethyltransferase 2 (SHMT2) in hepatocellular carcinoma

Tumour Biol. 2016 May;37(5):6813-21. doi: 10.1007/s13277-015-4506-8. Epub 2015 Dec 10.

Abstract

It has been reported that miR-615-5p was upregulated in hepatocellular carcinoma (HCC) preventing both growth and migration. However, the underlying mechanism by which miR-615-5p played a role in HCC remains unknown. Here, in our present study, to investigate the mechanism of miR-615-5p, bioinformatic prediction and luciferase reporter assay were employed to ascertain the downstream target of miR-615-5p finding that the serine hydromethyltransferase 2 (SHMT2) was the direct downstream target. Knockdown or overexpression of miR-615-5p can lead to increasing or decreasing expression of SHMT2 in HCC cells. Besides, knockdown or overexpression of SHMT2 can suppress or promote both proliferation and migration of HCC cells, indicating that miR-615-5p can directly and negatively regulate the SHMT2 in HCC cells. In addition, to understand the clinicopathological significance of SHMT2 expression in HCC, immunohistochemistry was performed. It was found that SHMT2 expression was significantly associated with poor prognosis and TNM stage. Together, our results for the first time showed that miR-615-5p prevents proliferation and migration through negatively regulating SHMT2 in HCC.

Keywords: Hepatocellular carcinoma (HCC); Migration; Proliferation; SHMT2; miR-615-5p.

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycine Hydroxymethyltransferase / chemistry
  • Glycine Hydroxymethyltransferase / genetics*
  • Glycine Hydroxymethyltransferase / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA Interference
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics

Substances

  • MIRN615 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Glycine Hydroxymethyltransferase
  • SHMT protein, human