Murakumo Yoshiki, Sakurai Yasutaka, Kato Takuya, Hashimoto Hiroshi, Ichinoe Masaaki
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Japan.
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8002, Japan.
Cancers (Basel). 2023 Mar 11;15(6):1721. doi: 10.3390/cancers15061721.
DNA repair and cell cycle regulation are potential biological fields to develop molecular targeting therapies for cancer. Human REV7 was originally discovered as a homologous molecule to yeast Rev7, which is involved in DNA damage response and mutagenesis, and as the second homolog of yeast Mad2, involved in the spindle assembly checkpoint. Although REV7 principally functions in the fields of DNA repair and cell cycle regulation, many binding partners of REV7 have been identified using comprehensive analyses in the past decade, and the significance of REV7 is expanding in various other biological fields, such as gene transcription, epigenetics, primordial germ cell survival, neurogenesis, intracellular signaling, and microbial infection. In addition, the clinical significance of REV7 has been demonstrated in studies using human cancer tissues, and investigations in cancer cell lines and animal models have revealed the greater impacts of REV7 in cancer biology, which makes it an attractive target molecule for cancer management. This review focuses on the functions of REV7 in human cancer and discusses the utility of REV7 for cancer management with a summary of the recent development of inhibitors targeting REV7.
DNA修复和细胞周期调控是开发癌症分子靶向治疗的潜在生物学领域。人类REV7最初被发现是酵母Rev7的同源分子,酵母Rev7参与DNA损伤反应和诱变,同时人类REV7也是酵母Mad2的第二个同源物,参与纺锤体组装检查点。尽管REV7主要在DNA修复和细胞周期调控领域发挥作用,但在过去十年中通过全面分析已鉴定出许多REV7的结合伙伴,并且REV7在其他各种生物学领域的重要性正在不断扩展,例如基因转录、表观遗传学、原始生殖细胞存活、神经发生、细胞内信号传导和微生物感染。此外,在使用人类癌症组织的研究中已证明REV7的临床意义,并且在癌细胞系和动物模型中的研究揭示了REV7在癌症生物学中的更大影响,这使其成为癌症治疗中有吸引力的靶标分子。本综述重点关注REV7在人类癌症中的功能,并讨论REV7在癌症治疗中的效用,同时总结靶向REV7抑制剂的最新进展。