Overexpression of myosin VI regulates gastric cancer cell progression

Gene. 2016 Nov 15;593(1):100-109. doi: 10.1016/j.gene.2016.08.015. Epub 2016 Aug 8.

Abstract

Myosin VI (MYO6) is a unique member of the myosin superfamily. Although it has been reported to participate in human cancer progression, the role of MYO6 in gastric cancer remains unclear. In this study, we found the expression of MYO6 gene was higher in gastric cancer tissues than in the normal tissues by Oncomine database mining and affects patient overall survival using the Kaplan-Meier plotter online analysis. Additionally, the expression levels of MYO6 were widely expressed in gastric cancer cells by quantitative real-time Polymerase Chain Reaction (qRT-PCR) and western blot assay. Then knockdown of MYO6 significantly suppressed the proliferation and colony formation abilities of AGS and MGC80-3 cells. Moreover, cell cycle analysis showed that inhibition of MYO6 induced cell cycle arrested in G0/G1 phase in AGS and MGC80-3 cells. Further analysis showed knockdown of MYO6 downregulated cell-cycle activators cyclin A and cyclin D1 and upregulated cell-cycle inhibitor p21, as determined by qRT-PCR and western blot analysis in MGC80-3 cells. Meanwhile, MYO6 inhibition significantly induced apoptosis in AGS and MGC80-3 cells. Also, knockdown of MYO6 increased the expression of apoptosis-related proteins Bax and cleaved Caspase-3, and decreased Bcl-2 expression by western blot analysis in MGC80-3 cells. In addition, MYO6 knockdown also inhibited cell migration ability in MGC80-3 cells. Taken together, our study indicates that MYO6 may play an important role in gastric cancer tumorigenesis and may serve as a potential therapeutic target in human gastric cancer.

Keywords: Gastric cancer; Myosin VI; Proliferation; Short hairpin RNA.

MeSH terms

  • Caspase 3 / biosynthesis
  • Caspase 3 / genetics
  • Cell Line, Tumor
  • Cyclin A / biosynthesis
  • Cyclin A / genetics
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • G1 Phase*
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Resting Phase, Cell Cycle*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Up-Regulation*
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics

Substances

  • BAX protein, human
  • BCL2 protein, human
  • CCND1 protein, human
  • Cyclin A
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • myosin VI
  • Cyclin D1
  • CASP3 protein, human
  • Caspase 3
  • Myosin Heavy Chains