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Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma
Cancer Science ( IF 4.5 ) Pub Date : 2023-12-11 , DOI: 10.1111/cas.16038 Hirotaka Kato 1 , Shinya Hayami 1 , Masaki Ueno 1 , Norihiko Suzaki 1 , Masashi Nakamura 1 , Tomohiro Yoshimura 1 , Atsushi Miyamoto 1 , Yoshinobu Shigekawa 1 , Ken-Ichi Okada 1 , Motoki Miyazawa 1 , Yuji Kitahata 1 , Shogo Ehata 2 , Ryuji Hamamoto 3 , Hiroki Yamaue 1 , Manabu Kawai 1
Cancer Science ( IF 4.5 ) Pub Date : 2023-12-11 , DOI: 10.1111/cas.16038 Hirotaka Kato 1 , Shinya Hayami 1 , Masaki Ueno 1 , Norihiko Suzaki 1 , Masashi Nakamura 1 , Tomohiro Yoshimura 1 , Atsushi Miyamoto 1 , Yoshinobu Shigekawa 1 , Ken-Ichi Okada 1 , Motoki Miyazawa 1 , Yuji Kitahata 1 , Shogo Ehata 2 , Ryuji Hamamoto 3 , Hiroki Yamaue 1 , Manabu Kawai 1
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Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.
中文翻译：
组蛋白甲基转移酶 SUV420H1/KMT5B 导致肝细胞癌预后不良
肝细胞癌（HCC）即使在根治性手术后，复发率也很高，预后也很差。多激酶抑制剂已应用于HCC患者，但其效果受到限制。本研究旨在阐明 SUV420H1/KMT5B（组蛋白 H4 20 位赖氨酸甲基转移酶之一）的临床影响，并阐明 HCC 进展的新机制。我们利用免疫组织化学分析 ( n = 350) 的 HCC 临床组织样本回顾性研究了 SUV420H1 的表达。然后，我们对 SUV420H1 进行了功能丧失分析，包括细胞周期分析、迁移测定、侵袭测定和用于体外基因本体 (GO) 通路分析的 RNA 序列，以及体内异种移植小鼠的动物实验。 SUV420H1 高分组 ( n = 154) 的 5 年总体预后和 2 年/5 年无病生存率均显着低于 SUV420H1 低分组 ( n = 196) ( p <分别为 0.001 和p < 0.05）。 SUV420H1-高分组病理学上较SUV420H1-低分组肿瘤体积更大、肿瘤更多、分化更差、血管侵犯更多。多变量分析表明，SUV420H1 高分是总体生存率最差的独立因素。 SUV420H1敲低可以抑制细胞周期从G1期到S期以及细胞侵袭。 GO通路分析显示SUV420H1有助于细胞增殖、细胞侵袭和/或转移。 SUV420H1的过度表达在临床上导致HCC预后不良，抑制SUV420H1可以在体外和体内抑制肿瘤的进展和侵袭；因此，对SUV420H1的进一步分析对于发现未来的分子靶向药物是必要的。
更新日期：2023-12-11
中文翻译：
组蛋白甲基转移酶 SUV420H1/KMT5B 导致肝细胞癌预后不良
肝细胞癌（HCC）即使在根治性手术后，复发率也很高，预后也很差。多激酶抑制剂已应用于HCC患者，但其效果受到限制。本研究旨在阐明 SUV420H1/KMT5B（组蛋白 H4 20 位赖氨酸甲基转移酶之一）的临床影响，并阐明 HCC 进展的新机制。我们利用免疫组织化学分析 ( n = 350) 的 HCC 临床组织样本回顾性研究了 SUV420H1 的表达。然后，我们对 SUV420H1 进行了功能丧失分析，包括细胞周期分析、迁移测定、侵袭测定和用于体外基因本体 (GO) 通路分析的 RNA 序列，以及体内异种移植小鼠的动物实验。 SUV420H1 高分组 ( n = 154) 的 5 年总体预后和 2 年/5 年无病生存率均显着低于 SUV420H1 低分组 ( n = 196) ( p <分别为 0.001 和p < 0.05）。 SUV420H1-高分组病理学上较SUV420H1-低分组肿瘤体积更大、肿瘤更多、分化更差、血管侵犯更多。多变量分析表明，SUV420H1 高分是总体生存率最差的独立因素。 SUV420H1敲低可以抑制细胞周期从G1期到S期以及细胞侵袭。 GO通路分析显示SUV420H1有助于细胞增殖、细胞侵袭和/或转移。 SUV420H1的过度表达在临床上导致HCC预后不良，抑制SUV420H1可以在体外和体内抑制肿瘤的进展和侵袭；因此，对SUV420H1的进一步分析对于发现未来的分子靶向药物是必要的。
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