CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1

Jingyu Liao; Zeyu Chen; Ruizhi Chang; Tong Yuan; Ganxun Li; Chang Zhu; Jingyuan Wen; Yi Wei; Zhao Huang; Zeyang Ding; Liang Chu; Junnan Liang; Bixiang Zhang

doi:10.7150/ijbs.85656

CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1

Int J Biol Sci. 2023 Oct 16;19(16):5218-5232. doi: 10.7150/ijbs.85656. eCollection 2023.

Authors

Jingyu Liao^{1

2

3}, Zeyu Chen^{1

2

3}, Ruizhi Chang^{1

2

3}, Tong Yuan^{1

2

3}, Ganxun Li^{1

2

3}, Chang Zhu^{1

2

3}, Jingyuan Wen^{1

2

3}, Yi Wei^{1

2

3}, Zhao Huang^{1

2

3}, Zeyang Ding^{1

2

3}, Liang Chu^{1

2

3}, Junnan Liang^{1

2

3}, Bixiang Zhang^{1

2

3}

Affiliations

¹ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China.
³ Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. In this study, we identified that CENPA was significantly up-regulated in HCC and highly expressed CENPA correlated with poor prognosis for HCC patients. Knockdown of CENPA inhibited HCC cell proliferation and tumor growth in vitro and in vivo. Mechanistically, CENPA transcriptionally activated and cooperated with YY1 to drive the expression of cyclin D1 (CCND1) and neuropilin 2 (NRP2). Moreover, we identified that CENPA can be lactylated at lysine 124 (K124). The lactylation of CENPA at K124 promotes CENPA activation, leading to enhanced expression of its target genes. In summary, CENPA function as a transcriptional regulator to promote HCC via cooperating with YY1. Targeting the CENPA-YY1-CCND1/NRP2 axis may provide candidate therapeutic targets for HCC.

Keywords: CENPA; HCC; Lactylation; YY1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / metabolism
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Centromere Protein A* / metabolism
Histones
Humans
Liver Neoplasms* / metabolism
YY1 Transcription Factor / genetics

Substances

Cell Cycle Proteins
Histones
YY1 protein, human
YY1 Transcription Factor
CENPA protein, human
Centromere Protein A