高级检索
当前位置: 首页 > 详情页

PA2G4 promotes the metastasis of hepatocellular carcinoma by stabilizing FYN mRNA in a YTHDF2-dependent manner

文献详情

资源类型:
WOS体系:
Pubmed体系:

收录情况: ◇ SCIE

单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, 1095 Jiefang Ave, Wuhan 430030, Peoples R China [2]Clin Med Res Ctr Hepat Surg Hubei Prov, Wuhan, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hubei Key Lab HepatoPancreat Biliary Dis, Wuhan, Peoples R China [4]Jianghan Univ, Sch Med, Wuhan Inst Biomed Sci, Wuhan, Peoples R China [5]Chinese Acad Med Sci, Key Lab Organ Transplantat, Minist Educ, Wuhan, Peoples R China [6]Chinese Acad Med Sci, Key Lab Organ Transplantat, Natl Hlth Commiss, Wuhan, Peoples R China [7]Chinese Acad Med Sci, Key Lab Organ Transplantat, Wuhan, Peoples R China
出处:
ISSN:

关键词: HCC m6A YTHDF2 FYN

摘要:
Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality. Advanced stage upon diagnosis and cancer metastasis are the main reasons for the dismal prognosis of HCC in large part. The role of proliferation associated protein 2G4 (PA2G4) in tumorigenesis and cancer progression has been widely investigated in various cancers. However, whether and how PA2G4 participates in HCC metastasis is still underexplored. Results We found that the mRNA and protein levels of PA2G4 were higher in HCC samples than in normal liver tissues, and high expression of PA2G4 in HCC was correlated with a poor prognosis, by an integrative analysis of immunohistochemistry (IHC), western blot and bioinformatic approach. Moreover, the expression of PA2G4 was elevated in HCC patients with metastases than those metastasis-free. Cell migration, invasion, phalloidin staining and western blot analyses demonstrated that PA2G4 promoted epithelial to mesenchymal transition (EMT) of HCC cells in vitro. And a lung metastasis animal model exhibited that PA2G4 enhanced metastatic ability of HCC cells in vivo. RNA-sequencing combined with dual luciferase reporter assay and evaluation of mRNA half-time indicated that PA2G4 increased FYN expression by stabilizing its mRNA transcript. Recovering the impaired FYN level induced by PA2G4 knockdown rescued the impeded cell mobilities. Furthermore, endogenous immunoprecipitation (IP) and in-situ immunofluorescence (IF) showed that YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) was the endogenous binding patterner of PA2G4. In addition, RNA binding protein immunoprecipitation (RIP) and anti- N6-methyladenosine immunoprecipitation (MeRIP) assays demonstrated that FYN mRNA was N6-methyladenosine (m6A) modified and bound with PA2G4, as well as YTHDF2. Moreover, the m6A catalytic ability of YTHDF2 was found indispensable for the regulation of FYN by PA2G4. At last, the correlation of expression levels between PA2G4 and FYN in HCC tissues was verified by IHC and western blot analysis. Conclusions These results indicate that PA2G4 plays a pro-metastatic role by increasing FYN expression through binding with YTHDF2 in HCC. PA2G4 may become a reliable prognostic marker or therapeutic target for HCC patients.

基金:
语种:
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2021]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
JCR分区:
出版当年[2020]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者:
第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, 1095 Jiefang Ave, Wuhan 430030, Peoples R China [2]Clin Med Res Ctr Hepat Surg Hubei Prov, Wuhan, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hubei Key Lab HepatoPancreat Biliary Dis, Wuhan, Peoples R China
通讯作者:
通讯机构: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, 1095 Jiefang Ave, Wuhan 430030, Peoples R China [2]Clin Med Res Ctr Hepat Surg Hubei Prov, Wuhan, Peoples R China [3]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hubei Key Lab HepatoPancreat Biliary Dis, Wuhan, Peoples R China
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:426 今日访问量:2 总访问量:410 更新日期:2025-04-01 建议使用谷歌、火狐浏览器 常见问题

版权所有:重庆聚合科技有限公司 渝ICP备12007440号-3 地址:重庆市两江新区泰山大道西段8号坤恩国际商务中心16层(401121)