Open Access

Silencing of keratin 17 by lentivirus‑mediated short hairpin RNA inhibits the proliferation of PANC‑1 human pancreatic cancer cells

  • Authors:
    • Peng Chen
    • Zhengchao Shen
    • Xiaosan Fang
    • Guannan Wang
    • Xiaoming Wang
    • Jun Wang
    • Shihang Xi
  • View Affiliations

  • Published online on: March 20, 2020     https://doi.org/10.3892/ol.2020.11469
  • Pages: 3531-3541
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Keratin 17 (KRT17) has been demonstrated to be a potential biological marker for the prediction of prognosis in particular types of cancer. The aim of the present study was to investigate the molecular mechanisms underlying the function of KRT17 in the pancreatic cancer (PAC) cell line PANC‑1 and the potential of KRT17 as a therapeutic target for PAC. KRT17 expression levels were analyzed using quantitative PCR and compared with histological data using bioinformatics tools in PAC samples and three human PAC cell lines. Cell proliferation was determined using an MTT assay, in addition to cell cycle distribution and apoptosis analysis using flow cytometry, colony formation assay using Giemsa staining and cell motility analysis using a Transwell migration assay. Tumor growth was evaluated in vivo in nude mice. The expression levels of a number of signaling molecules were measured to establish the potential mechanism by which silencing KRT17 expression affected PAC PANC‑1 cells. Increased levels of KRT17 expression were observed in human PAC compared with normal tissues, as well as in three human PAC cell lines (MIA PaCa‑2, PANC‑1 and KP‑3 cells) compared with the H6c7 human immortal pancreatic duct epithelial cell line. High expression levels of KRT17 in PAC samples were associated with poor overall survival (P=0.036) and disease‑free survival (P=0.017). Lentivirus‑mediated KRT17 silencing inhibited cell proliferation, colony formation and migration, but promoted apoptosis and resulted in cell cycle arrest in the G0/G1 phase in PANC‑1 cells. In addition, KRT17 knockdown inhibited in vivo tumor growth. KRT17 knockdown induced dysregulation of ERK1/2 and upregulation of the pro‑apoptotic Bcl‑2 protein Bad. In conclusion, the present study demonstrated that elevated KRT17 levels are positively associated with pancreatic cancer progression; KRT17 knockdown suppressed cell growth, colony formation, migration and tumor growth, and induced apoptosis and cell cycle arrest, affecting ERK1/2/Bad signaling. Therefore, the results of the present study suggested that KRT17 may be a potential target for the treatment of pancreatic cancer.

Related Articles

Journal Cover

May 2020
Volume 19 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Chen, P., Shen, Z., Fang, X., Wang, G., Wang, X., Wang, J., & Xi, S. (2020). Silencing of keratin 17 by lentivirus‑mediated short hairpin RNA inhibits the proliferation of PANC‑1 human pancreatic cancer cells. Oncology Letters, 19, 3531-3541. https://doi.org/10.3892/ol.2020.11469
MLA
Chen, P., Shen, Z., Fang, X., Wang, G., Wang, X., Wang, J., Xi, S."Silencing of keratin 17 by lentivirus‑mediated short hairpin RNA inhibits the proliferation of PANC‑1 human pancreatic cancer cells". Oncology Letters 19.5 (2020): 3531-3541.
Chicago
Chen, P., Shen, Z., Fang, X., Wang, G., Wang, X., Wang, J., Xi, S."Silencing of keratin 17 by lentivirus‑mediated short hairpin RNA inhibits the proliferation of PANC‑1 human pancreatic cancer cells". Oncology Letters 19, no. 5 (2020): 3531-3541. https://doi.org/10.3892/ol.2020.11469