CRIF1–CDK2 Interface Inhibitors: An Unprecedented Strategy for Modulation of Cell Radiosensitivity

Ran, Qian; Xiang, Yang; Stephen, Preyesh; Wu, Chun; Tang, Li; Lin, Szu-Yuan; Li, Zhongjun

doi:10.1021/jacs.8b10207

Cited by 11 publications

(16 citation statements)

References 22 publications

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“…[27] CDKs, such as CDK2, are critical for cell cycle regulation and have been implicated in the occurrence of cancer. [28] MMP-2 and MMP-9 are members of the MMP family and have been linked with tumor invasion and metastasis, while Bax, which is one of the BCL-2 family proteins, promotes cell apoptosis. [29,30] SOX4 can increase the protein level of cyclin D1 in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

SOX4 induces drug resistance of colorectal cancer cells by downregulating CYLD through transcriptional activation of microRNA‐17

Pan

Bao

et al. 2021

J Biochem & Molecular Tox

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Exposure to high doses of anticancer drugs can induce the emergence of a subpopulation of weakly proliferative and drug-tolerant cells. Drug tolerance can reduce the benefits obtained from canonical treatment and reduce the survival rate of patients. Regulation of SRY-related HMG box transcription factor 4 (SOX4) has been proved to affect drug sensitivity. The current study aimed to explore the role of SOX4 in drug resistance of colorectal cancer (CRC) cells as well as the related molecular mechanisms. Expression patterns of SOX4, microRNA-17 (miR-17), and CYLD in both CRC tissues and cells were determined with their relationship analyzed by bioinformatics analysis, dual-luciferase reporter gene assay, and ChIP.Loss-and gain-function assays were performed to ascertain the effect of SOX4, miR-17, and CYLD on biological cellular processes and drug resistance to 5-FU. SOX4 and miR-17 were found to be highly expressed while CYLD was poorly expressed in CRC tissues and cells. Silencing of SOX4 resulted in the suppression of cellular proliferation, invasion, migration as well as a reduction in CRC drug resistance. Mechanically, CYLD was specifically targeted by miR-17, while SOX4 upregulated the expression of miR-17. Functionally, SOX4 triggered drug resistance of CRC cells to 5-FU through the miR-17/CYLD axis. Taken together, the key findings of the present study provides evidence suggesting that SOX4 elevates miR-17 to decrease CYLD, thus inducing chemotherapy resistance of CRC cells.

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Section: Discussionmentioning

confidence: 99%

SOX4 induces drug resistance of colorectal cancer cells by downregulating CYLD through transcriptional activation of microRNA‐17

Pan

Bao

et al. 2021

J Biochem & Molecular Tox

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“…CRIF1 (MRPL64) can regulate the oxidative stress of irradiated bone marrow mesenchymal stem cells through phosphorylation of NRF2 Ser40 , which is helpful for the treatment of hemocytopenia, as well as multiple organ failures caused by hematopoietic dysfunction in the acute radiation syndrome [56]. CRIF1 (MRPL64) interacting with CDK2 can enhance the radio-sensitivity of tumor cells [133].…”

Section: Mrps Associated With Age and Other Related Mitochondrial Diseasesmentioning

confidence: 99%

Abnormal Expression of Mitochondrial Ribosomal Proteins and Their Encoding Genes with Cell Apoptosis and Diseases

Huang

Zhang

2020

IJMS

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Mammalian mitochondrial ribosomes translate 13 proteins encoded by mitochondrial genes, all of which play roles in the mitochondrial respiratory chain. After a long period of reconstruction, mitochondrial ribosomes are the most protein-rich ribosomes. Mitochondrial ribosomal proteins (MRPs) are encoded by nuclear genes, synthesized in the cytoplasm and then, transported to the mitochondria to be assembled into mitochondrial ribosomes. MRPs not only play a role in mitochondrial oxidative phosphorylation (OXPHOS). Moreover, they participate in the regulation of cell state as apoptosis inducing factors. Abnormal expressions of MRPs will lead to mitochondrial metabolism disorder, cell dysfunction, etc. Many researches have demonstrated the abnormal expression of MRPs in various tumors. This paper reviews the basic structure of mitochondrial ribosome, focuses on the structure and function of MRPs, and their relationships with cell apoptosis and diseases. It provides a reference for the study of the function of MRPs and the disease diagnosis and treatment.

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“…Previous studies indicated that CRIF1 may have a regulatory involvement in microenvironment-induced leukemia cell cycle arrest by acting as a CDK2 inhibitor [ 15 ]. Protein–protein docking studies showed that two potential binding sites on CRIF1 are involved in the accommodation of CDK2: a small and long α helix [ 16 ]. It is suggested that the CRIF1–CDK2 interface inhibitor could improve cellular radio sensitivity in the osteosarcoma (OS) cell lines by selectively enhancing arrest in the G2/M phase and apoptosis associated with CDK2 overactivation in these cells [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

CRIF1-CDK2 Interface Inhibitors Enhance Taxol Inhibition of the Lethal Triple-Negative Breast Cancer

Sang

Belmessabih

Wang

et al. 2022

Cancers

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Paclitaxel (taxol), a chemotherapeutic agent, remains the standard of care for the lethal triple-negative breast cancer (TNBC). However, over 50% of TNBC patients become resistant to chemotherapy and, to date, no solution is available. CR6-interacting factor 1 (CRIF1) is reported to act as a negative regulator of the cell cycle by interacting with cyclin-dependent kinase 2 (CDK2). In our study, two selective CRIF1–CDK2 interface inhibitors were used to investigate whether they could exert anti-proliferative activity on the TNBC cell lines. When combined with taxol treatment, these two inhibitors can advance the cells from G0/G1 to S and G2/M phases, producing irreparable damage to the cells, which then undergo apoptosis. Moreover, they enhanced the reduction in cell proliferation induced by taxol in TNBC cells, thereby improving sensitivity to taxol in these cell lines. Importantly, the inhibitors did not regulate the cell cycle in normal cells, indicating their high selectivity towards TNBC cells. Overall, the resistance to the anti-proliferative effects induced by taxol can be significantly reduced by the combined treatment with selective CRIF1–CDK2 interface inhibitors, making a conceptual advance in the CDK-related cancer treatment.

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CRIF1–CDK2 Interface Inhibitors: An Unprecedented Strategy for Modulation of Cell Radiosensitivity

Cited by 11 publications

References 22 publications

SOX4 induces drug resistance of colorectal cancer cells by downregulating CYLD through transcriptional activation of microRNA‐17

SOX4 induces drug resistance of colorectal cancer cells by downregulating CYLD through transcriptional activation of microRNA‐17

Abnormal Expression of Mitochondrial Ribosomal Proteins and Their Encoding Genes with Cell Apoptosis and Diseases

CRIF1-CDK2 Interface Inhibitors Enhance Taxol Inhibition of the Lethal Triple-Negative Breast Cancer

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