Impact of PIN1 Inhibition on Tumor Progression and Chemotherapy Sensitivity in Colorectal Cancer

J Gastrointest Cancer. 2022 Jun;53(2):299-310. doi: 10.1007/s12029-021-00600-6. Epub 2021 Feb 13.

Abstract

Background: Deregulated PIN1 is associated with cancer development and progression. Herein, for the first time, we evaluate the roles that PIN1 in tumorigenic characteristics of colorectal cancer (CRC) cells.

Methods: In this study, PIN1 expression was knocked down in SW-48 cells by synthetic small interfering RNA (siRNA). After confirming the knockdown of PIN1, cell viability, colony formation, apoptosis, autophagy, cancer stem cell (CSC)-related genes, CSC-related signaling pathways, cell migration, and 5-FU chemosensitivity were evaluated in vitro.

Results: Transfection of PIN1 siRNA into SW-48 cells inhibited cancer cell proliferation, migration, and increased apoptosis and autophagy. Transfected SW-48 cells had lower properties of CSCs through the inhibition of β-catenin and Notch1 gene expression. Moreover, inhibition of PIN1 enhanced the inhibitory effect of 5-FU on SW-48 cell proliferation.

Conclusion: Our results indicated that targeting of PIN1 serves as a promising therapeutic solution for the suppression of tumor progression processes in CRC.

Keywords: Apoptosis; Autophagy; CSCs; Chemosensitivity; Colorectal cancer; PIN1.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • NIMA-Interacting Peptidylprolyl Isomerase* / genetics
  • NIMA-Interacting Peptidylprolyl Isomerase* / metabolism
  • Neoplastic Stem Cells / metabolism
  • RNA, Small Interfering / metabolism

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • RNA, Small Interfering
  • PIN1 protein, human
  • Fluorouracil