Gastric Cancer

, Volume 20, Issue 6, pp 948–959 | Cite as

Knockdown of KRT17 by siRNA induces antitumoral effects on gastric cancer cells

  • Mihaela Chivu-Economescu
  • Denisa L. Dragu
  • Laura G. Necula
  • Lilia Matei
  • Ana Maria Enciu
  • Coralia Bleotu
  • Carmen C. Diaconu
Original Article
  • 373 Downloads

Abstract

Background

Keratin 17 (KRT17) was shown to be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of various cancer types. Our previous studies identified KRT17 as a possible biomarker for gastric cancer by gene microarray, with an elevated expression that occurred early during tumorigenesis and increased during tumor progression. Based on these findings, we aimed to investigate KRT17 biological functions in gastric adenocarcinoma and its possible use as a rational molecular target for anticancer therapy.

Methods

We used RNA interference-mediated knockdown of KRT17 expression and analyzed the effects on cell proliferation, cell migration, and signal transduction in two gastric cell lines (AGS and NCI-N87) in vitro and on xenograft growth in vivo.

Results

The functional analysis of KRT17 knockdown cell lines showed a decreased cell proliferation (with 42.36% ± 3.2%) and migration ability (with 37.2% ± 6.2%) relative to scrambled siRNA control. The in vivo tumorigenicity on nude mice exhibited a significant decrease in tumor weight with 69.14% in xenografts obtained from AGS cells and 84.43% in xeno-NCI-N87 tumors. The analysis on KRT17 knockdown outcome on intracellular signaling identifies AKT/mTOR as the main affected pathway that sustains proliferation and survival, and also the AMPKα1/CREB pathway that was recently shown to induce organ protection and antiinflammatory response.

Conclusions

Our results highlight KRT17 as a possible biomarker in gastric cancer promoting tumor growth, motility, and invasion, and suggest that KRT17 can be a valuable molecular target for development of anti-gastric cancer-specific therapies.

Keywords

Keratin 17 Biomarkers Gastric cancer Targeted therapy RNA interference 

Notes

Acknowledgements

This study was supported by structural funds from POS CCE O2.2.1. 433/2012, UEFISCDI PCCA PN II 133/2012 and OPERATIONAL COMPETITIVITATY PROGRAM 2014-2020 POC-A1-A1.1.4-E-2015/P_37_798/149/2016.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal studies

All institutional and national guidelines for the care and use of laboratory animals were followed.

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2017

Authors and Affiliations

  1. 1.Cellular and Molecular DepartmentStefan S. Nicolau Institute of VirologyBucharestRomania
  2. 2.Nicolae Cajal InstituteTitu Maiorescu UniversityBucharestRomania
  3. 3.Biochemistry-Proteomics DepartmentVictor Babes National Institute of PathologyBucharestRomania
  4. 4.Cell Biology and Histology DepartmentCarol Davila University of Medicine and PharmacyBucharestRomania

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