Page 73 - GPD-2-1

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Alkylation repair homolog 3-regulated

esophageal squamous cell carcinoma
associated long non-coding RNA 1 is

required for maintaining the stemness of
esophageal cancer

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Yuanbo Cui , Yanan Lou , Pengju Lv , and Wei Cao *
1 Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University,
Zhengzhou 450007, China
2 Department of Breast Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University,
Zhengzhou, 450007, China

Abstract

N -methyladenosine (m A) RNA modification represents one of the essential post-
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transcriptional modifications in gene expression regulation. Long non-coding
RNAs (lncRNAs) are involved in the development of malignant tumors, including
esophageal cancer (ESCA). However, whether m A can regulate that lncRNA in
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cancer cells remains unclear. ESCA cell lines TE1 and KYSE70 were used for functional
experiments. The mRNA and protein levels were detected by quantitative reverse
*Corresponding author: transcription polymerase chain reaction and Western blot, respectively. Colony
Wei Cao formation and tumor sphere formation assays were used for evaluating ESCA
(caowei7@zzu.edu.cn)
stemness. The m A modification on esophageal squamous cell carcinoma associated
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Citation: Cui Y, Lou Y, Lv P, et al., long non-coding RNA 1 (ESCCAL-1) transcript was examined by methylated RNA
2023, Alkylation repair homolog
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3-regulated esophageal squamous immunoprecipitation. In this study, we report that RNA m A demethylase alkylation
cell carcinoma associated long repair homolog 3 (ALKBH3)-mediated ESCCAL-1 is implicated in maintaining stem
non-coding RNA 1 is required cell-like properties of ESCA. Clinically, ESCCAL-1 was up-regulated in ESCA and
for maintaining the stemness of
esophageal cancer. Gene Protein Dis, positively correlated with tumor stage. In addition, patients with higher ESCCAL-1
2(1):305. expression in tumors had shorter median survival. Functionally, the knockdown of
https://doi.org/10.36922/gpd.305 ESCCAL-1 attenuated the stemness of ESCA cells as indicated by decreased sphere
Received: December 28, 2022 formation and colony formation capacities, while overexpression of ESCCAL-1
Accepted: February 21, 2023 elicits the opposite biological effects. Moreover, ESCCAL-1 manipulation positively
Published Online: March 13, 2023 regulated both mRNA and protein levels of KLF4 and CD44, two stemness-
Copyright: © 2023 Author(s). related markers. Mechanistically, ALKBH3 upregulated ESCCAL-1 expression
This is an Open Access article in an m A demethylation-dependent manner. Notably, the downregulation of
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distributed under the terms of the
Creative Commons Attribution ALKBH3 mimicked the effects of ESCCAL-1 deficiency on ESCA stemness, and this
License, permitting distribution, phenomenon is significantly reversed by the enforced expression of ESCCAL-1. Our
and reproduction in any medium, results revealed the role of m A-mediated ESCCAL-1 in ESCA self-renewal, which
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provided the original work is
properly cited. expands the understanding of lncRNA post-transcriptional modification in cancer
development.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
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published maps and institutional Keywords: ALKBH3; N -methyladenosine; ESCCAL-1; Stemness; Esophageal cancer
affiliations.

Volume 2 Issue 1 (2023) 1 https://doi.org/10.36922/gpd.305