The Clinical Significance of the Expression of FEN1 in Primary Osteosarcoma

Zhong, Guang‐Xian; Wang, Yunqing; Wei, Hongxiang; Chen, Mei‐Fang; Lin, Huangfeng; Huang, Zhen; Ji, Huang; Wang, Shenglin; Lin, Jianhua

doi:10.2147/ijgm.s335817

Cited by 5 publications

(6 citation statements)

References 31 publications

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“…It was documented that dysregulation of expression or mutation in FEN1 in normal cells leads to provoking various diseases, such as cancers [58]. Moreover, our data were conflicting with the literature supporting its overexpression that contributes to drug resistance and it suggests targeting this gene, which has been verified as an effective strategy in mono-or combination therapy for many cancers [59]. Our information is in contradiction with previous studies considering FEN1 as a marker of multiple metastatic tumors and poor prognosis [60] and is viewed as an effective target for tumor resistance treatment [61].…”

Section: Discussioncontrasting

confidence: 72%

The Curcumin Analog PAC Is a Potential Solution for the Treatment of Triple-Negative Breast Cancer by Modulating the Gene Expression of DNA Repair Pathways

Almalki,

Al-Amri,

Alrashed

et al. 2023

IJMS

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Breast Cancer (BC) is one of the most common and challenging cancers among females worldwide. Conventional treatments for oral cancer rely on the use of radiology and surgery accompanied by chemotherapy. Chemotherapy presents many side effects, and the cells often develop resistance to this chemotherapy. It will be urgent to adopt alternative or complementary treatment strategies that are new and more effective without these negative effects to improve the well-being of patients. A substantial number of epidemiological and experimental studies reported that many compounds are derived from natural products such as curcumin and their analogs, which have a great deal of beneficial anti-BC activity by inducing apoptosis, inhibiting cell proliferation, migration, and metastasis, modulating cancer-related pathways, and sensitizing cells to radiotherapy and chemotherapy. In the present study, we investigated the effect of the curcumin-analog PAC on DNA repair pathways in MCF-7 and MDA-MB-231 human breast-cancer cell lines. These pathways are crucial for genome maintenance and cancer prevention. MCF-7 and MDA-MB-231 cells were exposed to PAC at 10 µM. MTT and LDH assays were conducted to evaluate the effects of PAC on cell proliferation and cytotoxicity. Apoptosis was assessed in breast cancer cell lines using flow cytometry with annexin/Pi assay. The expression of proapoptotic and antiapoptotic genes was determined by RT-PCR to see if PAC is active in programming cell death. Additionally, DNA repair signaling pathways were analyzed by PCR arrays focusing on genes being related and confirmed by quantitative PCR. PAC significantly inhibited breast-cancer cell proliferation in a time-dependent manner, more on MDA-MB-231 triple-negative breast cancer cells. The flow cytometry results showed an increase in apoptotic activity. These data have been established by the gene expression and indicate that PAC-induced apoptosis by an increased Bax and decreased Bcl-2 expression. Moreover, PAC affected multiple genes involved in the DNA repair pathways occurring in both cell lines (MCF-7 and MDA-MB231). In addition, our results suggest that PAC upregulated more than twice 16 genes (ERCC1, ERCC2, PNKP, POLL, MPG, NEIL2, NTHL1, SMUG1, RAD51D, RAD54L, RFC1, TOP3A, XRCC3, XRCC6BP1, FEN1, and TREX1) in MDA-MB-231, 6 genes (ERCC1, LIG1, PNKP, UNG, MPG, and RAD54L) in MCF-7, and 4 genes (ERCC1, PNKP, MPG, and RAD54L) in the two cell lines. In silico analysis of gene–gene interaction shows that there are common genes between MCF-7 and MDA-MB-321 having direct and indirect effects, among them via coexpression, genetic interactions, pathways, predicted and physical interactions, and shared protein domains with predicted associated genes indicating they are more likely to be functionally related. Our data show that PAC increases involvement of multiple genes in a DNA repair pathway, this certainly can open a new perspective in breast-cancer treatment.

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Section: Discussioncontrasting

confidence: 72%

The Curcumin Analog PAC Is a Potential Solution for the Treatment of Triple-Negative Breast Cancer by Modulating the Gene Expression of DNA Repair Pathways

Almalki,

Al-Amri,

Alrashed

et al. 2023

IJMS

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“…15 This proliferative activityrelated property has also been noted in cancer cells, where FEN1 overexpression has been associated with accelerated progression and shorter survival periods. [16][17][18][19] Notably, an abnormal DNA damage repair process not only induces the production of neoantigens on the cell surface, 8 but also affects PD-L1 expression through the JAK/STAT1 signaling pathway and interferon stimulator genes (ISGs), 20,21 raising the question of whether interfering with FEN1 gene expression can simultaneously affect PD-L1 and HLA/MHC levels.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1

Wang

Sun

et al. 2023

Int J Oral Sci

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Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.

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“…In a previous study, Shang et al reported increased levels of sphingolipid and ceramides in patients with acute gout, suggesting that the onset of gout was related to the sphingolipid metabolism pathway [18]. Acute onset of gout is known to be related to gout crystals that stimulate the formation of NALP3 in ammasome by monocytes and promote the release of in ammatory factors (IL-2 and TNF-α) to act on joint synovium, which further causes in ammation expansion [19]. TNF-α is an in ammatory factor that can stimulate the production of sphingolipid by the mitochondria.…”

Section: Relationship Between Lipid Metabolism Pathway and Acute Atta...mentioning

confidence: 99%

Analysis the relationship of refractory gout between potential biomarkers and diet structure and lifestyle based on 1 H-NMR

Liang,

Chen,

Cheng

et al. 2023

Preprint

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Objective: We investigated the different between diet structure and life and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum 1H-NMR metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structure and exercise patterns. Methods: The present study employed a questionnaire survey to analyze 100 cases of refractory gout patients and 79 healthy volunteers with respect to their diet structure and the lifestyle. Accordingly, we used 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). NMR results were further combined with pattern recognition and multivariate statistics, and potential biomarkers were searched. The results were further combined with creatinine, adiponectin, and so on the correlation between the above results were analyzed. Results: Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of D‐glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease. Conclusion: Recurrent refractory gout and formation of tophus may be related to the diet structure and lifestyle between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response.

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The Clinical Significance of the Expression of FEN1 in Primary Osteosarcoma

Cited by 5 publications

References 31 publications

The Curcumin Analog PAC Is a Potential Solution for the Treatment of Triple-Negative Breast Cancer by Modulating the Gene Expression of DNA Repair Pathways

The Curcumin Analog PAC Is a Potential Solution for the Treatment of Triple-Negative Breast Cancer by Modulating the Gene Expression of DNA Repair Pathways

Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1

Analysis the relationship of refractory gout between potential biomarkers and diet structure and lifestyle based on 1 H-NMR

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