Open Access

Thapsigargin promotes colorectal cancer cell migration through upregulation of lncRNA MALAT1

  • Authors:
    • Xia Jiang
    • Dongyun Li
    • Guiqi Wang
    • Jue Liu
    • Xingkai Su
    • Weifang Yu
    • Yuanyuan Wang
    • Congjie Zhai
    • Yuegeng Liu
    • Zengren Zhao
  • View Affiliations

  • Published online on: February 13, 2020     https://doi.org/10.3892/or.2020.7502
  • Pages: 1245-1255
  • Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third most common tumor in the world; however, the role and mechanism of endoplasmic reticulum (ER) stress in CRC metastasis remains largely unclear. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is a long non‑coding RNA (lncRNA), which has previously been associated with CRC metastasis. It has been suggested that ER stress pathways regulate lncRNA expression; however, the effect of ER stress on MALAT1 expression in cancer is unknown. The present study aimed to investigate the relationship between ER stress pathways, MALAT1 expression and cell migration in CRC cells. ER stress was induced by thapsigargin (TG); low dose TG induced the migration of HT29 and HCT116 cells, but not SW1116 and SW620 cells. This effect was associated with increased expression levels of MALAT1, as the knockdown of MALAT1 prevented TG‑induced cell migration. TG‑induced MALAT1 expression was associated with inositol‑requiring enzyme 1 (IRE1) expression and activation of the protein kinase R (PKR)‑like ER kinase (PERK) signaling pathway. X‑box‑binding protein 1 (XBP1) and activating transcription factor 4 (ATF4) binding sites were predicted to be located in the MALAT1 gene promoter regions and the expression of MALAT1 was positively associated with XBP1 and ATF4 expression levels in CRC tissue samples. Thus, these findings indicated that ER stress may promote the migration of CRC cells and contribute to the progression of CRC through the activation of the IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways. In conclusion, to the best of our knowledge, this study is the first report that lncRNA MALAT1 expression is regulated by the IRE1/XBP1 pathway in CRC.

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April 2020
Volume 43 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Jiang, X., Li, D., Wang, G., Liu, J., Su, X., Yu, W. ... Zhao, Z. (2020). Thapsigargin promotes colorectal cancer cell migration through upregulation of lncRNA MALAT1. Oncology Reports, 43, 1245-1255. https://doi.org/10.3892/or.2020.7502
MLA
Jiang, X., Li, D., Wang, G., Liu, J., Su, X., Yu, W., Wang, Y., Zhai, C., Liu, Y., Zhao, Z."Thapsigargin promotes colorectal cancer cell migration through upregulation of lncRNA MALAT1". Oncology Reports 43.4 (2020): 1245-1255.
Chicago
Jiang, X., Li, D., Wang, G., Liu, J., Su, X., Yu, W., Wang, Y., Zhai, C., Liu, Y., Zhao, Z."Thapsigargin promotes colorectal cancer cell migration through upregulation of lncRNA MALAT1". Oncology Reports 43, no. 4 (2020): 1245-1255. https://doi.org/10.3892/or.2020.7502