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Heat-Shock Protein A12A Is a Novel PCNA-binding Protein and Promotes Hepatocellular Carcinoma Growth

Heat-Shock Protein A12A Is a Novel PCNA-binding Protein and Promotes Hepatocellular Carcinoma Growth

Hao Cheng, Xiaofei Cao, Xinxu Min, Xiaojin Zhang, Qiuyue Kong, Qian Mao, Rongrong Li, Bin Xue, Lei Fang, Li Liu, Zhengnian Ding

FEBS J. 2020 Mar 3.

PMID: 32128976

Abstract:

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Proliferating cell nuclear antigen (PCNA) plays a pivotal role in cancer development and progression. However, the long-term dismal prognosis of HCC mandates more investigation to identify novel regulators in HCC pathogenesis. Heat-shock protein A12A (HSPA12A) encodes a novel member of the HSP70 family. Here, we report that HCC cells showed increased HSPA12A expression, and overexpression of HSPA12A promoted HCC growth and angiogenesis in mice. Gain- and loss-of-functional studies demonstrated that the proliferation of HCC HepG2 cells, as well as β-catenin expression and nuclear translocation, was promoted by HSPA12A overexpression, but in turn suppressed by HSPA12A knockdown. HSPA12A did not impact PCNA expression; however, mass spectrometry and co-immunoprecipitation immunoblotting analysis revealed that HSPA12A directly binds to PCNA and promotes its trimerization, which is an essential functional conformation of PCNA for carcinogenesis. Importantly, PCNA inhibition by PCNA-I1 reversed the HSPA12A-mediated HepG2 cell differentiation. These findings indicate that HSPA12A is a novel regulator of HCC cell proliferation and tumor growth through binding to PCNA for its trimerization. HSPA12A inhibition might represent a viable strategy for the management of HCC in humans.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1364915489	PCNA-I1		1364915-48-9	Price

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