Downregulation of Ascl2 Promotes Cell Apoptosis by Enhancing Autophagy in Colorectal Cancer Cells

Overview

Journal J Gastrointest Oncol

Date 2021 May 20

PMID 34012655

Citations 4

Authors

Huipeng Wang

Tao Ye

Yuankun Cai

Wenjie Chen

Hongwei Xie

Chongwei Ke

Affiliations

Soon will be listed here.

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer, according to recently published literature. While the incidence and the mortality of CRC has decreased due to effective cancer screening measures, there has been an increase in the number of young patients diagnosed with colon cancer due to unclear reasons. As a target molecule of the Wnt signaling pathway, Ascl2 is an important marker of CRC stem cells and plays an important role in maintaining the nature of colon cancer stem/precursor cells. However, the role of Ascl2 in autophagy in CRC cells is rarely elucidated.

Methods: In this study, we found that Ascl2 was increased in CRC compared with adjacent tissue. Downregulation of Ascl2 in CRC cells could suppress proliferation and invasion, and induce apoptosis, of CRC cells. Moreover, we found that autophagy-relative protein LC3 increased after Ascl2 knockdown. Furthermore, we treated CRC cells with autophagy inhibitors 3-MA (3-Methyladenine) and CQ (Chloroquine).

Results: The results showed that autophagy inhibitors could prevent apoptosis, which was induced by Ascl2 knockdown. Finally, we confirmed that the downregulation of Ascl2 in CRC cells could alleviate the pathological process by xenograft experiment.

Conclusions: Our findings indicated that si-Ascl2 (small/short interfering) exerted a tumor suppression function in CRC by inducing autophagic cell death, and suggest that Ascl2 targeted therapy represents a novel strategy for CRC treatment.

Citing Articles

Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer.

Orlandi G, Roncucci L, Carnevale G, Sena P Int J Mol Sci. 2023; 24(12).

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Diagnostic genes and immune infiltration analysis of colorectal cancer determined by LASSO and SVM machine learning methods: a bioinformatics analysis.

Li Y, Meng K, Yang G, Liu B, Li C, Zhang J J Gastrointest Oncol. 2022; 13(3):1188-1203.

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Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.

Zhao H, Ming T, Tang S, Ren S, Yang H, Liu M Mol Cancer. 2022; 21(1):144.

PMID: 35836256 PMC: 9281132. DOI: 10.1186/s12943-022-01616-7.

DPEP1 promotes drug resistance in colon cancer cells by forming a positive feedback loop with ASCL2.

Zeng C, Qi G, Shen Y, Li W, Zhu Q, Yang C Cancer Med. 2022; 12(1):412-424.

PMID: 35670012 PMC: 9844606. DOI: 10.1002/cam4.4926.

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