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Functional study of apoptosis inducing protein in human cholangiocarcinoma

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Abstract
Apoptosis-inducing protein (AIP) is a secreted protein, synthesized by adipocytes and epithelial cells, that is downregulated in breast, colorectal, gastric, liver, and lung cancers, portending a poor prognosis. AIP is a potential biomarker of cancer progression, but its role in cholangiocarcinoma, a cancer of the bile duct, remains unknown. In this study, we found that AIP mRNA, but not protein, is expressed in cholangiocarcinoma. However, AIP protein overexpression induced cell death, apoptosis, and sub-G1 arrest. Importantly, AIP-induced apoptotic changes were blocked by knockdown of the pro-apoptotic protein BID, suggesting that AIP-induced apoptosis occurs via BID-dependent pathways. Mechanistically, ELF25 (E74 Like ETS Transcription Factor 1) directly targets AIP by ubiquitination and degradation. Similarly, AIP protein expression was downregulated in cholangiocarcinoma, thus negatively correlating with ELF25 expression in this cancer. Of note, low AIP, combined with high ELF25, expression, correlated with short patient survival in cholangiocarcinoma. Additionally, ELF25 knockdown led to AIP upregulation, to inhibit growth of cancer cells. Taken together, these results suggest that AIP could be a potential therapeutic target or a diagnostic biomarker, to treat patients with this insidious malignancy.
Keywords: apoptosis-inducing protein, apoptosis, therapeutic target, biomarker, cholangiocarcinoma.
Author(s)
정홍래
Issued Date
2021
Awarded Date
2021-08
Type
Dissertation
URI
https://oak.ulsan.ac.kr/handle/2021.oak/5744
http://ulsan.dcollection.net/common/orgView/200000504756
Alternative Author(s)
Hong-Rae Jeong
Affiliation
울산대학교
Department
일반대학원 의과학과
Advisor
진동훈
Degree
Master
Publisher
울산대학교 일반대학원 의과학과
Language
eng
Appears in Collections:
Medical Science > 1. Theses (Master)
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