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.
基金:
National Natural Science Foundation of China [82172971, 31671348, 82203809]; Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province [CXPJJH12000001-2020317]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan, 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
共同第一作者:
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Hepat Surg Ctr, Wuhan, 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):
Liao Jingyu,Chen Zeyu,Chang Ruizhi,et al.CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1[J].INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES.2023,19(16):5218-5232.doi:10.7150/ijbs.85656.
APA:
Liao, Jingyu,Chen, Zeyu,Chang, Ruizhi,Yuan, Tong,Li, Ganxun...&Zhang, Bixiang.(2023).CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,19,(16)
MLA:
Liao, Jingyu,et al."CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 19..16(2023):5218-5232