Dataset Information

ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner.

ABSTRACT: Epigenetic dysregulation of cell cycle is a hallmark of tumorigenesis in multiple cancers, including hepatocellular carcinoma (HCC). Nonetheless, the epigenetic mechanisms underlying the aberrant cell cycle signaling and therapeutic response remain unclear. Here, we used an epigenetics-focused CRISPR interference screen and identified ACTR5 (actin-related protein 5), a component of the INO80 chromatin remodeling complex, to be essential for HCC tumor progression. Suppression of ACTR5 activated CDKN2A expression, ablated CDK/E2F-driven cell cycle signaling, and attenuated HCC tumor growth. Furthermore, high-density CRISPR gene tiling scans revealed a distinct HCC-specific usage of ACTR5 and its interacting partner IES6 compared to the other INO80 complex members, suggesting an INO80-independent mechanism of ACTR5/IES6 in supporting the HCC proliferation. Last, our study revealed the synergism between ACTR5/IES6-targeting and pharmacological inhibition of CDK in treating HCC. These results indicate that the dynamic interplay between epigenetic regulators, tumor suppressors, and cell cycle machinery could provide novel opportunities for combinational HCC therapy.

SUBMITTER: Xu X

PROVIDER: S-EPMC9788768 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner.

Xu Xiaobao X Chan Anthony K N AKN Li Mingli M Liu Qiao Q Mattson Nicole N Pangeni Pokharel Sheela S Chang Wen-Han WH Yuan Yate-Ching YC Wang Jinhui J Moore Roger E RE Pirrotte Patrick P Wu Jun J Su Rui R Müschen Markus M Rosen Steven T ST Chen Jianjun J Yang Lu L Chen Chun-Wei CW

Science advances 20221223 51

Epigenetic dysregulation of cell cycle is a hallmark of tumorigenesis in multiple cancers, including hepatocellular carcinoma (HCC). Nonetheless, the epigenetic mechanisms underlying the aberrant cell cycle signaling and therapeutic response remain unclear. Here, we used an epigenetics-focused CRISPR interference screen and identified ACTR5 (actin-related protein 5), a component of the INO80 chromatin remodeling complex, to be essential for HCC tumor progression. Suppression of ACTR5 activated C ...[more]

PMID: 36563143

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Dataset Information

ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner.

Publications

ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner.

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