Reducing protein regulator of cytokinesis 1 as a prospective therapy for hepatocellular carcinoma

Cell Death & Disease
Xinran LiuKun Huang

Abstract

Proteins that bind to microtubule are important for cell cycle, and some of these proteins show oncogenic characteristics with mechanisms not fully understood. Herein we demonstrate overexpression of protein regulator of cytokinesis 1 (PRC1), a microtubule-associated regulator of mitosis, in human hepatocellular carcinoma (HCC). Moreover, upregulated PRC1 is associated with lower survival rates of HCC patients. Mechanistically, reducing PRC1 blocks mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent manner, and acts synergistically with microtubule-associated agents (MTAs) to suppress p53-wt or p53-null HCC cells in a p53- or p14ARF-dependent manner; while overexpressing PRC1 increases the resistance of HCC to taxol. A combined treatment of taxol/shPRC1 results in 90% suppression of tumor growth in subcutaneous HCC xenograft models. In orthotopic xenograft mice, reducing PRC1 significantly alleviates HCC development and hepatic injury. Together, our results suggest a dual-mitotic suppression approach against HCC by combining MTAs with cytokinesis inhibition, which blocks mitosis at both metaphase and telophase.

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Citations

Jul 26, 2019·Biological Reviews of the Cambridge Philosophical Society·Zhen-Yu SheMing-Hui Lu
Aug 17, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Jeyapal SugeedhaShweta Tyagi
Jan 29, 2019·Frontiers in Cell and Developmental Biology·Weimei RuanUttam Surana
Apr 27, 2021·Experimental Biology and Medicine·Yiting QiaoJianxiang Chen
Jun 16, 2021·Biochemical Pharmacology·Alfonso Serrano-Del ValleIsabel Marzo

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Methods Mentioned

BETA
confocal microscopy
transfection
xenograft
xenografts
PCR
reverse transcription PCR

Software Mentioned

SPSS
Calcusyn

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