Long Noncoding RNA 01534 Maintains Cancer Stemness by Downregulating Endoplasmic Reticulum Stress Response in Colorectal Cancer

Authors

Momoko Ichihara
Hidekazu Takahashi
Naohiro Nishida
Cristina Ivan
Daisuke Okuzaki
Yuhki Yokoyama
Masahisa Ohtsuka
Norikatsu Miyoshi
Mamoru Uemura
Shinji Tanaka
George Adrian Calin
Masaki Mori
Yuichiro Doki
Hidetoshi Eguchi
Hirofumi Yamamoto

Publication Date

5-1-2023

Journal

Annals of Gastroenterological Surgery

Abstract

Background: Studies have shown that cancer stemness and the endoplasmic reticulum (ER) stress response are inversely regulated in colorectal cancer (CRC), but the mechanism has not been fully clarified. Long noncoding RNAs (lncRNAs) play key roles in cancer progression and metastasis. In this study we investigated lncRNA 01534 (LINC01534) as a possible modulator between cancer stemness and ER stress response.

Methods: In vitro experiments using CRC cell lines were performed to explore a possible role of LINC01534. The expression of LINC01534 in clinical CRC samples was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization.

Results: Silencing LINC01534 led to suppression of cell proliferation, invasiveness, and cell cycle progression at the G2-M phase, and promoted apoptosis. Moreover, we found that silencing LINC01534 suppressed cancer stemness, while it activated the ER stress response, especially through the PERK/eIF2α signaling pathway. In situ hybridization revealed LINC01534 was expressed in tumor cells and upregulated in CRC tissues compared with normal epithelium. A survival survey indicated that high LINC01534 expression was significantly associated with shorter overall survival in 187 CRC patients.

Conclusion: This is the first report on LINC01534 in human cancer. Our findings suggest that LINC01534 may be an important modulator of the maintenance of cancer stemness and suppression of the ER stress response, and that it could be a novel prognostic factor in CRC.

Keywords

cancer stemness, colorectal cancer, endoplasmic reticulum stress, LINC01534, long noncoding RNA

DOI

10.1002/ags3.12649

PMID

37152770

PMCID

PMC10154865

PubMedCentral® Posted Date

12-29-2022

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes