FEN1 (Flap Structure-Specific Endonuclease 1)

Furthermore, FEN1 is associated with immune microenvironment regulation, and in some cases, may be associated with immunotherapy response. In LIHC models, experimental validation revealed that FEN1 stimulates tumorigenesis by stimulating proliferation, migration, and genomic instability.

Finally, the duplex FA-eLCR successfully detected the BCR/ABL1p210 transcripts in patients with chronic myeloid leukemia (CML) and monitored the change of transcripts during treatment, with 100 % concordance to reverse transcription-quantitative polymerase chain reaction, highlighting its high potential in the early diagnosis and minimal residual disease (MRD) monitoring of CML. This work presents a novel strategy to address nonspecific amplification in LCR and introduces a cost-effective, highly sensitive platform for molecular diagnosis in clinical setting.

In addition, the successful detection application in lysates of cancer cells demonstrates the potential of FCT-CRISPR for clinical use. This work establishes a sensitive, accurate, and mix-and-read platform for monitoring FEN1 activity and offers a promising tool for the early diagnosis of FEN1-related diseases.

This study demonstrates that atrazine promotes carcinogenesis by dysregulating conserved networks governing genomic stability, cell proliferation, metabolic adaptation, and immune microenvironment remodeling, providing a mechanistic framework linking aquatic atrazine exposure to multi-organ carcinogenesis and nominating HSD17B8-associated pathways for therapeutic intervention. These findings underscore the imperative for enhanced environmental monitoring of atrazine contamination.

Knockdown of FEN1 reversed the suppression of CD8+ T cell activation and antitumor immunity caused by NAA40 overexpression. This study demonstrates NAA40 promotes OSCC progression via enhancing FEN1 transcription and suppressing CD8+ T cell function, suggesting that NAA40 may serve as a novel prognostic marker and therapeutic target for OSCC.

FEN1 rs174538 A>G, FEN1 rs4246215 T>G, APEX1 rs3136817 T>C, and XRCC1 rs25487 C>T are associated with Wilms tumor susceptibility, which provides potential molecular markers for the early diagnosis of Wilms tumor.

Furthermore, we demonstrate that combined inhibition of these factors with MSC778 induces synergistic killing of cancer cells. Together these data highlight FEN1 inhibition as an attractive precision oncology strategy either as monotherapy or as a combination therapy with a broad range of current and next generation DDR-targeting agents.

Targeting this compensatory mechanism could provide new therapeutic strategies to selectively impair cancer cell survival under pre-existed replication stress. XPF is recruited to DNA replication forks in mouse or human cells of functional deficiency of FEN1 due to genetic mutations or chemical inhibition.XPF gene deficiency or chemical inhibition results in accumulation of 3' flaps and replicative DNA single-stranded breaks.Functional deficiency of XPF and FEN1 displays a synergy in inducing genome instability and cell death in human cancer cells.

By exploiting FEN1's unique substrate recognition properties, early-stage cancers can be detected via liquid biopsy or protein-focused assays. Collectively, this review underscores FEN1 as a promising biomarker and a multifaceted target for cancer interception and treatment, while also emphasizing the need for further mechanistic exploration and translational validation of FEN1-directed strategies.

Delactylation of these proteins significantly hinders the formation of FEN1-RAD1-RAD9A-HUS1 complex, thereby leading to dysfunction of NHEJ and increasing the sensitivity of cancer cells to cisplatin. In summary, this work identifies LDHA lactylation as a critical mechanism for accelerating the progression of LUAD and reveals how this lactylation influenced cisplatin sensitivity of LUAD cells, which deepen the understanding of lactylation-mediated tumor progression and provide a potential new anticancer strategy.

This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development.

Furthermore, Exonuclease 1 and PCNA partially compensate for the loss of Rad27 in rDNA stabilization. These findings highlight the importance of proper Okazaki fragment maturation in the maintenance of rDNA stability.