Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1. At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites. However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket. Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs. The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.

Objective To study hematotoxic effect of formaldehyde in mice.Methods Sixty healthy KM mice were randomly divided into a control group and three formaldehyde treated groups named a low level group,a moderate level group and high level group.Themice in the experimental groups were exposed to formaldehyde by intraperitoneal injection,once a day,for three weeks at the dose of 0.2,2.0 and 20 mg/kg bw respectively.Five mice were sacrificed at the 1st,2nd,3rd week of formaldehyde treatment and the blood samples were collected.The red blood cell counts,white blood cell counts and the hemoglobin content in the blood in mice were determined.Results During the experimental period,the body weight of mice in low level group at the 1st and 3rd week decreased significantly compared with the control group.The organ coefficient of the kidney in the moderate level group,high level group at the 1st week were higher than that of control group.The organ coefficient of the spleen in moderate level group at the 2nd week,in all three formaldehyde treated groups at the 3rd week was lower than that of control group.The organ coefficient of the heart in high level group at the 3rd week also decreased markedly in comparison to that of control group.The hemoglobin content in high level group at the 3rd week was lower than that of the control group.The red blood cell counts in three experiment groups at the 1st week and in high level group at the 2nd week decreased markedly compared with the control group.The white blood cell counts were seen much lower in low level group at the first two weeks,in moderate level group at the 1st week and in high level group in the experimental period compared with the control group.Conclusion Formaldehyde exposure has some hematotoxic effects in mice.