|Table of Contents|

Overexpression of breast cancer suppressor gene KRT17 promotes apoptosis and arrests cell cycle by activating p53 signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 17
Page:
3180-3189
Research Field:
Publishing date:

Info

Title:
Overexpression of breast cancer suppressor gene KRT17 promotes apoptosis and arrests cell cycle by activating p53 signaling pathway
Author(s):
CHEN Duo; HU Ming; ZHOU Hairui; ZHANG Xuesong
Plastic Surgery Department,School of Clinical Medicine,Jiamusi University,Heilongjiang Jiamusi 154007,China.
Keywords:
breast cancer; keratin 17; prognosis; p53 signaling pathway; cell growth
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.17.004
Abstract:
Objective:To investigate the expression and prognostic significance of keratin 17（KRT17) in breast cancer（BC) and its effect on the growth of cancer cells and its mechanism.Methods:Based on the BC data collected by the Cancer Genome Atlas（TCGA),differential expression genes and prognostic related genes were screened,and the target gene KRT17 was obtained by intersection.UALCAN,Human Protein Mapping（HPA) and TISCH2 databases were used to analyze the levels of KRT17 mRNA and protein in various cancers,the expression and localization of KRT17 in BC tissues,and the expression of KRT17 in tumor microenvironment,respectively.The correlation between KRT17 expression and prognosis in different datasets was also analyzed using the bc-GenExMiner v5.0 database.Next,the effects of KRT17 overexpression on the growth of MDA-MB-231 and MCF7 cells were examined,and the effects of KRT17 on the growth of BC cell lines were verified by genome-wide knockout and knockdown library screening data,and the regulatory effects of KRT17 on the growth of xenografts in nude mice were verified in vivo.Finally,flow cytometry was used to detect the regulation of overexpression of KRT17 on cell cycle and apoptosis,and the function of KRT17 was analyzed by GSEA enrichment.RT-qPCR and Western blotting were used to reveal the molecular mechanism of KRT17 promoting cancer growth.Results:The expression of KRT17 was heterogeneous in different tumors.The mRNA and protein levels of KRT17 in BC were significantly down-regulated（P＜0.001,P＜0.001).KRT17 protein was mainly located in the cytoplasm and cell membrane of cancer cells,and KRT17 was expressed in various cells in the tumor microenvironment.Low expression of KRT17 was a poor prognostic factor for BC（all P＜0.01),and overexpression of KRT17 could significantly inhibit the growth of MDA-MB-231 and MCF7 cells（P＜0.01,P＜0.01).Knockout or knockdown of KRT17 promoted the growth of multiple BC cell lines such as MDA-MB-231 and MCF7,and overexpression of KRT17 inhibited tumor volume in nude mouse xenografts（P＜0.001).Overexpression of KRT17 significantly promoted apoptosis（P＜0.001) and arrested G1 phase of the cell cycle（P＜0.01).The molecular results showed that p53 signaling pathway partially mediated the regulation of KRT17 overexpression on apoptosis and cell cycle.Conclusion:Low expression of KRT17 in BC is not conducive to the prognosis of patients,overexpression of KRT17 promotes apoptosis and retards cell cycle by activating p53 pathway,and KRT17 is a potential tumor suppressor gene.

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Memo

Memo:
黑龙江省自然科学基金项目（编号：LH2021H104）
Last Update: 2024-07-31