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Considering the connection between the Fanconi anemia (FA) signaling pathway and tumor development, we aim to investigate the links between the FA gene expression and the survival prognosis of acute myeloid leukemia (AML) patients. Our study begins by identifying two distinct clusters of pediatric AML patients. Following the batch matching of the TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts, the samples were divided into a training set and an internal validation set. A Lasso regression modeling analysis was performed to identify five signatures: BRIP1, FANCC, FANCL, MAD2L2, and RFWD3. The AML samples were stratified into high- and low-risk groups by evaluating the risk scores. The AML high-risk patients showed a poorer overall survival prognosis. To predict the survival rates, we developed an FA Nomogram incorporating risk score, gender, age, and French–American–British classification. We further utilized the BEAT-AML cohort for the external validation of FA-associated prognostic models and observed good clinical validity. Additionally, we found a correlation between DNA repair, cell cycle, and peroxide-related metabolic events and FA-related high/low risk or cluster 1/2. In summary, our novel FA-associated prognostic models promise to enhance the prediction of pediatric AML prognosis.

Tudor-SN (Tudor staphylococcal nuclease), also known as p100 or SND1 (Staphylococcal nuclease and Tudor domain containing 1), is a structurally conserved protein with diverse functions. Emerging evidence indicates that Tudor-SN plays an essential role in both physiological and pathological processes. Under physiological conditions, Tudor-SN regulates DNA transcription, RNA splicing, RNA stability, RNA interference, and RNA editing, and it is essential for a series of cellular biological events, such as cell cycle progression, cell metabolism, and cell survival, in response to harmful stimuli; thus, Tudor-SN functions as a “friend” to the body. However, Tudor-SN is highly expressed in most tumor cells. As an oncoprotein, Tudor-SN is closely associated with the initiation, development, and metastasis of tumors; thus, Tudor-SN functions as a “foe” to the body. What is the potential mechanism by which Tudor-SN switches from its role as “friend” to its role as “foe”? In this study, we review and summarize the available evidence regarding Tudor-SN protein structure, expression, modification, and mutation to present a novel model of Tudor-SN role switching. This review provides a comprehensive insight into the functional significance of the Tudor-SN protein under physiological and pathological conditions as well as corresponding therapeutic strategies that target Tudor-SN.

The mechanisms that regulate cell-cycle arrest of cardiomyocytes during heart development are largely unknown. We have previously identified Tudor staphylococcal nuclease (Tudor-SN) as a cell-cycle regulator and have shown that its expression level was closely related to cell-proliferation capacity. Herein, we found that Tudor-SN was highly expressed in neonatal mouse myocardia, but it was lowly expressed in that of adults. Using Data Base of Transcription Start Sites (DBTSS), we revealed that Tudor-SN was a terminal oligo-pyrimidine (TOP) mRNA. We further confirmed that the translational efficiency of Tudor-SN mRNA was controlled by the mammalian target of rapamycin complex 1 (mTORC1) pathway, as revealed via inhibition of activated mTORC1 in primary neonatal mouse cardiomyocytes and activation of silenced mTORC1 in adult mouse myocardia; additionally, this result was recapitulated in H9c2 cells. We also demonstrated that the downregulation of Tudor-SN in adult myocardia was due to inactivation of the mTORC1 pathway to ensure that heart growth was in proportion to that of the rest of the body. Moreover, we revealed that Tudor-SN participated in the mTORC1-mediated regulation of cardiomyocytic proliferation, which further elucidated the correlation between Tudor-SN and the mTORC1 pathway. Taken together, our findings suggest that the translational efficiency of Tudor-SN is regulated by the mTORC1 pathway in myocardia and that Tudor-SN is involved in mTORC1-mediated regulation of cardiomyocytic proliferation and cardiac development. [ABSTRACT FROM AUTHOR]

Members of the growth arrest–specific 2 (GAS2) protein family consist of a putative actin‐binding (CH) domain and a microtubule‐binding (GAR) domain and are considered miniversions of spectraplakins. There are four members in the GAS2 family, viz. GAS2, GAS2L1, GAS2L2 and GAS2L3. Although GAS2 is defined as a family of growth arrest–specific proteins, the significant differences in the expression patterns, interaction characteristics and biological issues or diseases among the different GAS2 family members have not been systemically reviewed to date. Therefore, we summarized the available evidence on the structures and functions of GAS2 family members. This review facilitates a comprehensive molecular understanding of the involvement of the GAS2 family members in an array of biological processes, including cytoskeleton reorganization, cell cycle, apoptosis and cancer development. [ABSTRACT FROM AUTHOR]