TY - JOUR
T1 - TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1
AU - Wang, Xiaobo
AU - Shi, Jiawei
AU - Huang, Mingming
AU - Chen, Jiehong
AU - Dan, Jia
AU - Tang, Yunhua
AU - Guo, Zhiyong
AU - He, Xiaoshun
AU - Zhao, Qiang
N1 - Funding Information:
Supported by grants as follows: National Natural Science Foundation of China (81570587 and 81700557), the Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007 and 2017B030314018), Guangdong Provincial Natural Science Funds for Major Basic Science Culture Project (2015A030308010), and Guangdong Provincial Funds for High-end Medical Equipment (2020B1111140003), and Science and Technology Program of Guangzhou (201704020150), the Natural Science Foundations of Guangdong province (2016A030310141 and 2020A1515010091), Young Teachers Training Project of Sun Yat-Sen University (K0401068) and Colin New Star of Sun Yat-Sen University (R08027).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/3
Y1 - 2023/3
N2 - Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan–Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.
AB - Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan–Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.
UR - http://www.scopus.com/inward/record.url?scp=85149522660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85149522660&partnerID=8YFLogxK
U2 - 10.1038/s41419-023-05687-2
DO - 10.1038/s41419-023-05687-2
M3 - Article
C2 - 36872411
AN - SCOPUS:85149522660
VL - 14
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 3
M1 - 179
ER -